Setup

rm(list=ls())
knitr::opts_knit$set(root.dir = '~/OneDrive - University College London/Projects/Ostridge_PanAf/baypass/analysing_baypass_output/baypass_aux/') 

Parameters

subsps=c('all', 'ce', 'w')
env_data='f_over_sum_known_trees'
habitat_col=c('freq_trees_Forest'='black')
chr21=TRUE
flanks=1000

FPRs were assigned in ./baypass_aux/scripts/f_over_sum_known_trees/f_over_sum_known_trees.baypass_aux_candidate.Rmd.

This script looks at the functions of the few SNPs with the strongest evidence of selection.

Library

library(data.table)
options(datatable.fread.datatable=FALSE)
library(dplyr)
library(viridis) 

source("../scripts/baypass_tools.R")
source("scripts/baypass_aux_tools.R")
source("../baypass_core/scripts/distribution_of_candidates_in_the_genome_tools-cov_cor.R")

Read in data

## - all 
## - ce 
## - w
## Warning in scan(file = file, what = what, sep = sep, quote = quote, dec = dec,
## : number of items read is not a multiple of the number of columns

Select top genes

There are two main ways this can be done and I allow for either using the ‘mode’ option.

1- Select top SNPs the treat the genes they belong to as the top genes

2- Select the top genes.

There are also two main statistics that I could use to select the top SNPs/genes

1- FPR

2- Bayes Factor

I could also use Beta (correlation coefficient) to select SNPs/genes with the largest effect sizes.

mode='snp'
top_n=100

Select top N SNPs/genes by minium FPR

top_snps=list()
cat("Mode: ", mode)
## Mode:  snp
for(subsp in subsps){
  for(cov in covs){
    betai_fpr.tmp=betai_fpr[[subsp]][betai_fpr[[subsp]]$COVARIABLE_name==cov,]
    betai_fpr.tmp=betai_fpr.tmp[order(betai_fpr.tmp$fpr, -betai_fpr.tmp$`BF(dB).median`, -abs(betai_fpr.tmp$M_Beta.median)),]
    if(mode=='snp'){
      betai_fpr.tmp=merge(head(unique(betai_fpr.tmp[,c('chr', 'pos')]), top_n), betai_fpr.tmp, by=c('chr', 'pos'), all.x=TRUE)
    }else if(mode=='gene'){
      betai_fpr.tmp=betai_fpr.tmp[!is.na(betai_fpr.tmp$gene),]
      betai_fpr.tmp=head(unique(betai_fpr.tmp[,c('gene')]), top_n)
    }else{
      stop("'mode' must be set to 'gene' or 'snp'")
    }
    top_snps[[subsp]][[cov]]=betai_fpr.tmp
  }
}

Select top N SNPs/genes by top BF per coverage bin

This issue with using minimum FPR to select the top SNPs is that the minimum possible FPR is determined by the number of null SNPs in that coverage bin. For the purpose of selecting the top SNPs, it may be best to select the highest BF values per bin instead.

I first select the number of top SNPs/genes I want then work out how many SNPs are in each coverage bin and use this to select the top SNPs proportionally.

if(mode=='snp'){
  cols=c('chr', 'pos')
}else if(mode=='gene'){
  cols='gene'
}else{
  stop("'mode' must be set to 'gene' or 'snp'")
}
top=list()
for(subsp in subsps){
  for(cov in covs){
    # Get number of SNPs per bin
    n_per_bin=table(unique(betai_fpr[[subsp]][,c(cols, 'coverage_bin')])$coverage_bin)
    # Get total number of SNPs
    tot=sum(n_per_bin)
    # Get the top number of SNPs to select from each bin
    top_n_per_bin=round(top_n*n_per_bin/tot)
    bins=unique(betai_fpr[[subsp]]$coverage_bin)
    for(bin in bins[order(bins)]){
      betai_fpr.tmp=betai_fpr[[subsp]][betai_fpr[[subsp]]$COVARIABLE_name==cov & betai_fpr[[subsp]]$coverage_bin==bin,]
      betai_fpr.tmp=betai_fpr.tmp[order(-betai_fpr.tmp$`BF(dB).median`, -abs(betai_fpr.tmp$M_Beta.median)),]
      if(mode=='gene'){
        # Remove non-geneic 
        betai_fpr.tmp=betai_fpr.tmp[!is.na(betai_fpr.tmp[[cols]]),]
      }
      # Select data for top SNPs/genes
      betai_fpr.tmp=merge(head(unique(betai_fpr.tmp[,cols, drop=FALSE]), top_n_per_bin[bin]), betai_fpr.tmp, by=cols, all.x=TRUE)
      if(mode=='gene'){
        # Report the SNP within the gene with the highest BF
        betai_fpr.tmp=betai_fpr.tmp %>% group_by(gene) %>% top_n(1, `BF(dB).median`)
      }
      if(bin==1){
        top[[subsp]][[cov]]=betai_fpr.tmp
      }else{
        top[[subsp]][[cov]]=rbind(top[[subsp]][[cov]], betai_fpr.tmp)
      }
    }
    # Order output
    top[[subsp]][[cov]]=top[[subsp]][[cov]][order(-top[[subsp]][[cov]]$`BF(dB).median`, top[[subsp]][[cov]]$fpr),]
    top[[subsp]][[cov]]$BF_rank=rank(-top[[subsp]][[cov]]$`BF(dB).median`, ties.method="min")
    top[[subsp]][[cov]]$fpr_rank=rank(top[[subsp]][[cov]]$fpr, ties.method="min")
    print(head(top[[subsp]][[cov]][!is.na(top[[subsp]][[cov]]$gene),c('BF(dB).median', 'M_Beta.median', 'gene')], 10))
    
  }
  # Volcano plot
  aux_volcano.v2(top[[subsp]][[cov]], 
                   x='M_Beta.median', y='`BF(dB).median`', colour_col='COVARIABLE_name', colours=habitat_col[covs], log_density=FALSE)
  # Manhatten plot
  manhattan_plot(top[[subsp]][[cov]], stat="log_fpr", cov_col="black", title=paste(subsp, "; ", cov, "top 100 SNPs")) 
  # Env vs AF plot
  tmp.list=list()
  tmp.list[[subsp]]=top[[subsp]][[cov]]
  run_env_vs_AF.v4(tmp.list, cov.in, allele.freq[subsp], stats=c("M_P", "M_Pstd"), fprs=1)
}
##    BF(dB).median M_Beta.median    gene
## 79      46.93736    0.17895837  CLSTN3
## 46      41.47486    0.18234756   ARVCF
## 63      38.43384    0.18751901  ADAM18
## 85      37.57740    0.15373262   BEST2
## 48      37.32474   -0.23479515  SH3RF1
## 31      36.64199    0.14600827   FKBP3
## 32      36.64199    0.14600827  PRPF39
## 1       35.69221    0.15023802 TSPAN18
## 2       35.69221    0.15023802 TP53I11
## 87      34.76361    0.09494603  IL10RB

##    BF(dB).median M_Beta.median   gene
## 34      52.96448     0.2021141   PCP2
## 35      52.96448     0.2021141 PET100
## 36      52.96448     0.2021141   XAB2
## 61      52.96448     0.1454179  DOCK5
## 24      49.95201    -0.1946517  DZIP1
## 50      49.95201    -0.2628328  WDR19
## 56      49.95201     0.2258253 ZCCHC9
## 62      49.95201     0.2338510   ASPH
## 86      49.95201    -0.2493903 MOGAT1
## 91      49.95201     0.2301506 SLC6A7

##    BF(dB).median M_Beta.median   gene
## 80      40.89057     0.1733309  BEST2
## 73      36.23802     0.1707913 CLSTN3
## 63      35.36143     0.2185704 ADAM18
## 62      32.65331     0.1675469 SEMA3A
## 29      31.98373    -0.2146088  ZNF48
## 30      31.98373    -0.2146088  SEPT1
## 37      31.82971     0.1986122   USP6
## 4       30.74346     0.2199250   MYH9
## 78      30.27637    -0.1979228   RFFL
## 18      29.95158     0.1773350  PANX1

Write gowinda files

if(chr21){
  suffix=paste0(".non-genic_",flanks,"bp.flanks")
}else{
  suffix="-cov_cor"
}
for(subsp in subsps){
  if(subsp=='all'){subsp.file=''}else{subsp.file=paste0(".", subsp)}
  if(subsp=='n'){miss.pop=0}else{miss.pop=0.3}
    # Write Gowinda input files
  for(cov in unique(betai_fpr[[subsp]]$COVARIABLE_name)){
    ## Both
    write.table(unique(top[[subsp]][[cov]][, c("chr", "pos")]), 
                paste0("../../../gowinda/baypass_aux/output/gowinda_input/snp_files/", env_data,"/",subsp,".", env_data,"-",cov,".top",top_n,"snps" ,suffix),
                col.names=F, row.names=F, sep="\t")
    ## Positive beta
    write.table(unique(top[[subsp]][[cov]][top[[subsp]][[cov]]$M_Beta.median>0, c("chr", "pos")]), 
                paste0("../../../gowinda/baypass_aux/output/gowinda_input/snp_files/", env_data,"/",subsp,".", env_data,"-",cov,".top",top_n,"snps" ,suffix, ".pos_beta"),
                col.names=F, row.names=F, sep="\t")
    ## Negative beta
    write.table(unique(top[[subsp]][[cov]][top[[subsp]][[cov]]$M_Beta.median<0, c("chr", "pos")]), 
                paste0("../../../gowinda/baypass_aux/output/gowinda_input/snp_files/", env_data,"/",subsp,".", env_data,"-",cov,".top",top_n,"snps" ,suffix, ".neg_beta"),
                col.names=F, row.names=F, sep="\t")
  }
}

Investigate top genes

Overlap

# Re-structure data for venn diagram plotting
top_2=list()
for(cov in covs){
  for(subsp in subsps){
    tmp=top[[subsp]][[cov]]
    tmp$COVARIABLE_name=cov
    if(nrow(tmp)>0){
      top_2[[subsp]]=rbind(top_2[[subsp]], tmp)
    }else{
      top_2[[subsp]]=tmp
    }
  }
}
candidate_overlap.v3(top_2, fprs=1)

GeneCards Data

I started a conversation with the people at GeneCards through the chat window at https://www.genecards.org/ (you can also email ). It took a long time but I finally got them to send me a csv with gene names and descriptions of each gene. This means that rather than manually searching each gene name I can just search this file.

Things to look out for

Pathways involved in adaptation to desserts in other mammals

These underlie adaptation to stresses such as dehydration and temperature regulation which are stresses we might expect in savanna too.

  • Fat metabolism

    • Water produced from fat metabolism can be utilised to reduce dehydration stress

    • Fat reserves provide insulation and can be used when food is scarce

  • Insulin signalling

  • Thyroid system

  • Radiation - pigmentation

  • Kidneys

    • Arachidonic acid metabolism pathway
  • Blood pressure

#dessert_genes=c("NETO1", "SLC2A12", "KCNJ2", "KNG1", "SLC12A2", "SLC2A9", "CYP2", "CPY2J2", "UCP1", "KCNJ2", "KNG1")

# From figure 1D Rocha et al. (2021)
dessert_genes=unique(c("GDF10", "APPL2", "BMP2", "BBS1", "PRKAB1", "NETO1", "KCNJ2", "TRHDE", "KCNJ2", "KNG1", "NR3C2", "ATP12A", "SLC8A1", "KCNJ5", 
                       "TRHDE", "GPX3", "ERP44", "SLC4A4", "PPRSS8", "CYP2J2", "APPL1", "APPL2", "SLLCA12", "SLC2A9", "CYP2J", "CYP2E", "GPX3", "CYP4V2", 
                       "SLCA1", "SLC12A3", "SLC2A9", "SLC8A1", "SLC47A1"))
  
for(subsp in subsps){
  cat(subsp, "\n")
  print(top_2[[subsp]][top_2[[subsp]]$gene %in% dessert_genes, c('chr', 'pos', 'BF(dB).median', 'COVARIABLE_name', 'M_Beta.median', 'fpr', 'gene')])
}
## all 
## [1] chr             pos             BF(dB).median   COVARIABLE_name
## [5] M_Beta.median   fpr             gene           
## <0 rows> (or 0-length row.names)
## ce 
##     chr     pos BF(dB).median        COVARIABLE_name M_Beta.median          fpr
## 116   4 9922071      46.93736 f_over_sum_known_trees     -0.216599 0.0001992032
##       gene
## 116 SLC2A9
## w 
## [1] chr             pos             BF(dB).median   COVARIABLE_name
## [5] M_Beta.median   fpr             gene           
## <0 rows> (or 0-length row.names)
Other hypotheses
  • More nocturnal activity in hotter areas might lead to selection for vison - we have some evidence for this in the gene set enrichment for candidates in central-eastern

  • Differences in diets - digestive enzymes

  • Pathogen/immune related genes - more pathogens in forest

  • Reproductive traits

    • Higher population densities in forest could lead to more sexual selection?

Look at all genes

top_genes_func=list()

for(subsp in subsps){
  cat("-", subsp, "\n")
  for(cov in covs){
    cat("--", cov, "\n")
    top_genes=toupper(top[[subsp]][[cov]]$gene)
    top_genes=unique(top_genes[!is.na(top_genes)])
    # Select the top genes from the GeneCards database
    top_genes_func[[subsp]][[cov]]=gene_cards[gene_cards$symbol %in% top_genes,]
    for(gene in top_genes){
      top.tmp=top[[subsp]][[cov]][top[[subsp]][[cov]]$gene%in%gene, c("BF(dB).median", "M_Beta.median")]
      top_func.tmp=top_genes_func[[subsp]][[cov]][top_genes_func[[subsp]][[cov]]$symbol==gene,]
      cat("---", gene, "; BF(dB)=", top.tmp$`BF(dB).median`, "; M_beta=", top.tmp$M_Beta.median,"\n")
      cat("   ", unique(top_func.tmp$name),"\n")
      #print(strtrim(top_genes_func[[subsp]][[cov]][top_genes_func[[subsp]][[cov]]$symbol==gene,]$description, 300))
      print(top_func.tmp$description[!grepl("^Reaction=|^EC |^Kinetic parameters: ", top_func.tmp$description)])
      cat("\n")
    }
    # Which genes are missing a description?
    cat("---", subsp, " missing genes\n")
    print(top_genes[!(top_genes %in% gene_cards$symbol)])
  }
  cat("\n\n\n\n")
}
## - all 
## -- f_over_sum_known_trees 
## --- CLSTN3 ; BF(dB)= 46.93736 31.39442 ; M_beta= 0.1789584 0.1198365 
##     Calsyntenin 3 
## [1] "May modulate calcium-mediated postsynaptic signals. Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2-mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation."
## 
## --- ARVCF ; BF(dB)= 41.47486 ; M_beta= 0.1823476 
##     ARVCF Delta Catenin Family Member 
## [1] "Drosophila armadillo repeat gene homolog,catenin family,ubiquitously expressed,involved in protein-protein interaction at adherens juctions,deleted in the velocardiofacial syndrome"
## [2] "Involved in protein-protein interactions at adherens junctions."                                                                                                                     
## 
## --- ADAM18 ; BF(dB)= 38.43384 33.99027 32.30704 ; M_beta= 0.187519 0.2144211 0.1063716 
##     ADAM Metallopeptidase Domain 18 
## [1] "Sperm surface membrane protein that may be involved in spermatogenesis and fertilization. This is a non catalytic metalloprotease-like protein (By similarity)."
## 
## --- BEST2 ; BF(dB)= 37.5774 ; M_beta= 0.1537326 
##     Bestrophin 2 
## [1] "Forms calcium-sensitive chloride channels. Permeable to bicarbonate."
## 
## --- SH3RF1 ; BF(dB)= 37.32474 ; M_beta= -0.2347952 
##     SH3 Domain Containing Ring Finger 1 
## [1] "Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination (PubMed:15659549, PubMed:20696164). Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-independent endocytosis (PubMed:19710010). Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4(+) and CD8(+) T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4(+) T-cells and the activation of MAPK8/JNK1 in CD8(+) T-cells. Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (By similarity)."
## [2] "(Microbial infection) Plays an essential role in the targeting of HIV-1 Gag to the plasma membrane, this function is dependent on it's RING domain, and hence it's E3 ligase activity."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
## 
## --- FKBP3 ; BF(dB)= 36.64199 ; M_beta= 0.1460083 
##     FKBP Prolyl Isomerase 3 
## [1] "FK506-binding protein 3,T cell binding protein FKBP-25 for the immunosuppressive agents FK506-rapamycin ,with intrinsic peptidyl-prolyl cis-trans isomerase activity"                                                                                            
## [2] "FK506- and rapamycin-binding proteins (FKBPs) constitute a family of receptors for the two immunosuppressants which inhibit T-cell proliferation by arresting two distinct cytoplasmic signal transmission pathways. PPIases accelerate the folding of proteins."
## [3] "Inhibited preferentially by rapamycin over FK506."                                                                                                                                                                                                               
## 
## --- PRPF39 ; BF(dB)= 36.64199 ; M_beta= 0.1460083 
##     Pre-MRNA Processing Factor 39 
## [1] "Involved in pre-mRNA splicing."
## 
## --- TSPAN18 ; BF(dB)= 35.69221 ; M_beta= 0.150238 
##      
## character(0)
## 
## --- TP53I11 ; BF(dB)= 35.69221 ; M_beta= 0.150238 
##     Tumor Protein P53 Inducible Protein 11 
## [1] "By p53/TP53."
## 
## --- IL10RB ; BF(dB)= 34.76361 ; M_beta= 0.09494603 
##     Interleukin 10 Receptor Subunit Beta 
## [1] "interleukin 10,receptor beta,cytokine receptor family II,member 4 (CRF2-4)"                                                                                                                                                                                                                                                                                                                                                           
## [2] "Shared cell surface receptor required for the activation of five class 2 cytokines: IL10, IL22, IL26, IL28, and IFNL1. The IFNLR1/IL10RB dimer is a receptor for the cytokine ligands IFNL2 and IFNL3 and mediates their antiviral activity. The ligand/receptor complex stimulate the activation of the JAK/STAT signaling pathway leading to the expression of IFN-stimulated genes (ISG), which contribute to the antiviral state."
## 
## --- SLC22A10 ; BF(dB)= 34.62548 ; M_beta= 0.1530514 
##      
## character(0)
## 
## --- SLC22A25 ; BF(dB)= 34.62548 ; M_beta= 0.1530514 
##      
## character(0)
## 
## --- DDX18 ; BF(dB)= 34.62548 ; M_beta= 0.1229987 
##     DEAD-Box Helicase 18 
## [1] "Probable RNA-dependent helicase."
## 
## --- MICAL1 ; BF(dB)= 34.36094 ; M_beta= 0.1905949 
##     Microtubule Associated Monooxygenase, Calponin And LIM Domain Containing 1 
## [1] "Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization (By similarity). In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2) (PubMed:21864500, PubMed:26845023). Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments. Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4. Involved in regulation of lamina-specific connectivity in the nervous system such as the development of lamina-restricted hippocampal connections. Through redox regulation of the actin cytoskeleton controls the intracellular distribution of secretory vesicles containing L1/neurofascin/NgCAM family proteins in neurons, thereby regulating their cell surface levels (By similarity). May act as Rab effector protein and play a role in vesicle trafficking."
## 
## --- SMPD2 ; BF(dB)= 34.36094 ; M_beta= 0.1905949 
##     Sphingomyelin Phosphodiesterase 2 
## [1] "Catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these 2 cellular events independently. Also hydrolyzes sphingosylphosphocholine. Hydrolyze 1-acyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PC) and 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-platelet-activating factor)."
## [2] "pH dependence: Optimum pH is 6.5-7.5.;"                                                                                                                                                                                                                                                                                                                                                                                            
## 
## --- STXBP5 ; BF(dB)= 34.36094 ; M_beta= 0.1455832 
##     Syntaxin Binding Protein 5 
## [1] "Plays a regulatory role in calcium-dependent exocytosis and neurotransmitter release. Inhibits membrane fusion between transport vesicles and the plasma membrane. May modulate the assembly of trans-SNARE complexes between transport vesicles and the plasma membrane. Inhibits translocation of GLUT4 from intracellular vesicles to the plasma membrane. Competes with STXBP1 for STX1 binding (By similarity)."
## 
## --- IGSF10 ; BF(dB)= 33.99027 ; M_beta= 0.166629 
##     Immunoglobulin Superfamily Member 10 
## [1] "Involved in the control of early migration of neurons expressing gonadotropin-releasing hormone (GNRH neurons) (By similarity). May be involved in the maintenance of osteochondroprogenitor cells pool (By similarity)."
## 
## --- UNC5B ; BF(dB)= 33.6467 ; M_beta= 0.1035903 
##     Unc-5 Netrin Receptor B 
## [1] "Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion (By similarity). Functions as netrin receptor that negatively regulates vascular branching during angiogenesis. Mediates retraction of tip cell filopodia on endothelial growth cones in response to netrin (By similarity). It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (PubMed:12598906). Mediates apoptosis by activating DAPK1. In the absence of NTN1, activates DAPK1 by reducing its autoinhibitory phosphorylation at Ser-308 thereby increasing its catalytic activity (By similarity)."
## [2] "By p53/TP53."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
## 
## --- RHOD ; BF(dB)= 33.53751 ; M_beta= 0.1531253 
##     Ras Homolog Family Member D 
## [1] "Involved in endosome dynamics. May coordinate membrane transport with the function of the cytoskeleton. Involved in the internalization and trafficking of activated tyrosine kinase receptors such as PDGFRB. Participates in the reorganization of actin cytoskeleton; the function seems to involve WHAMM and includes regulation of filopodia formation and actin filament bundling. Can modulate the effect of DAPK3 in reorganization of actin cytoskeleton and focal adhesion dissolution."
## 
## --- SPC25 ; BF(dB)= 33.53751 ; M_beta= 0.0688434 
##     SPC25 Component Of NDC80 Kinetochore Complex 
## [1] "Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:14699129, PubMed:14738735). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:14738735, PubMed:14699129). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020)."
## 
## --- NOSTRIN ; BF(dB)= 33.53751 ; M_beta= 0.0688434 
##     Nitric Oxide Synthase Trafficking 
## [1] "Multivalent adapter protein which may decrease NOS3 activity by inducing its translocation away from the plasma membrane."
## 
## --- SRXN1 ; BF(dB)= 33.53751 ; M_beta= 0.09632171 
##     Sulfiredoxin 1 
## [1] "Contributes to oxidative stress resistance by reducing cysteine-sulfinic acid formed under exposure to oxidants in the peroxiredoxins PRDX1, PRDX2, PRDX3 and PRDX4. Does not act on PRDX5 or PRDX6. May catalyze the reduction in a multi-step process by acting both as a specific phosphotransferase and a thioltransferase."
## 
## --- ANK3 ; BF(dB)= 33.0263 ; M_beta= 0.1605332 
##     Ankyrin 3 
## [1] "ankyrin 3,non erythrocytic,intermediate filament associated protein (IFAP,type III),expressed in the axonal initial segment and Ranvier nodes in the central and peripheral nervous system"                                                                                                                                                                                                                                               
## [2] "In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments. Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (PubMed:23903368)."
## [3] "[Isoform 5]: May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin."                                                                                                                                                                                                                                                                                                                                    
## 
## --- DNAJB9 ; BF(dB)= 32.93031 ; M_beta= 0.06198444 
##     DnaJ Heat Shock Protein Family (Hsp40) Member B9 
## [1] "Co-chaperone for Hsp70 protein HSPA5/BiP that acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (By similarity). J domain-containing co-chaperones stimulate the ATPase activity of Hsp70 proteins and are required for efficient substrate recognition by Hsp70 proteins (PubMed:18400946). In the unstressed endoplasmic reticulum, interacts with the luminal region of ERN1/IRE1 and selectively recruits HSPA5/BiP: HSPA5/BiP disrupts the dimerization of the active ERN1/IRE1 luminal region, thereby inactivating ERN1/IRE1 (By similarity). Also involved in endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins. Required for survival of B-cell progenitors and normal antibody production (By similarity)."
## 
## --- THAP5 ; BF(dB)= 32.93031 ; M_beta= 0.06198444 
##     THAP Domain Containing 5 
## [1] "Has sequence-specific DNA-binding activity and can function as transcriptional repressor (in vitro) (PubMed:21110952). May be a regulator of cell cycle: THAP5 overexpression in human cell lines causes cell cycle arrest at G2/M phase (PubMed:19502560)."
## [2] "Up-regulated both in response to UV light treatment and cisplatin, agents that cause DNA damage (at protein level)."                                                                                                                                        
## 
## --- PNPLA8 ; BF(dB)= 32.93031 ; M_beta= 0.06198444 
##     Patatin Like Phospholipase Domain Containing 8 
## [1] "Calcium-independent phospholipase A2, which promotes cellular membrane hydrolysis and prostaglandin production (PubMed:10744668, PubMed:15695510). Catalyzes the hydrolysis of the sn-2 position of glycerophospholipids, phosphytidylserine and to a lower extent phosphatidylcholine (PubMed:10744668). Cleaves membrane phospholipids (PubMed:15695510). Participates in the generation of lipid second messengers through the mobilization of arachidonic acid in response to cellular stimuli. Synthesizes 2-arachidonoyl lysophosphatidylcholine, a key branch point metabolite in eicosanoid signaling (PubMed:15908428). Participates in the lipid plasticity of myocardium, plays a role in the generation of signaling metabolites and has a prominent effect on the modulaton of energy storage and utilization (PubMed:17213206). Essential for maintaining efficient bioenergetic mitochondrial function through tailoring mitochondrial membrane lipid metabolism and composition (By similarity)."
## [2] "pH dependence: Optimum pH is 8.0.;"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
## [3] "Inhibited by E-6-bromomethylene-3-1-naphthalenyl-2H-tetrahydropyran-2-one (BEL)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
## 
## --- SEMA3A ; BF(dB)= 32.8362 ; M_beta= 0.191074 
##     Semaphorin 3A 
## [1] "Involved in the development of the olfactory system and in neuronal control of puberty. Induces the collapse and paralysis of neuronal growth cones. Could serve as a ligand that guides specific growth cones by a motility-inhibiting mechanism. Binds to the complex neuropilin-1/plexin-1."
## [2] "semaphorin 3A,secreted,repellent of the nerve growth cone guidance"                                                                                                                                                                                                                            
## 
## --- OSBPL6 ; BF(dB)= 32.74389 ; M_beta= 0.197897 
##     Oxysterol Binding Protein Like 6 
## [1] "Regulates cellular transport and efflux of cholesterol (PubMed:26941018). Plays a role in phosphatidylinositol-4-phophate (PI4P) turnover at the neuronal membrane (By similarity). Binds via its PH domain PI4P, phosphatidylinositol-4,5-diphosphate, phosphatidylinositol-3,4,5-triphosphate, and phosphatidic acid (By similarity). Weakly binds 25-hydroxycholesterol (PubMed:17428193)."
## [2] "By acetylated low-density lipoprotein."                                                                                                                                                                                                                                                                                                                                                       
## 
## --- TMEM167B ; BF(dB)= 32.39133 ; M_beta= 0.2240599 
##     Transmembrane Protein 167B 
## [1] "Involved in the early part of the secretory pathway."
## 
## --- STAP1 ; BF(dB)= 32.39133 ; M_beta= 0.08429985 
##     Signal Transducing Adaptor Family Member 1 
## [1] "In BCR signaling, appears to function as a docking protein acting downstream of TEC and participates in a positive feedback loop by increasing the activity of TEC."
## 
## --- GPD2 ; BF(dB)= 32.14272 ; M_beta= 0.08120009 
##     Glycerol-3-Phosphate Dehydrogenase 2 
## [1] "Calcium-responsive mitochondrial glycerol-3-phosphate dehydrogenase which seems to be a key component of the pancreatic beta-cell glucose-sensing device."
## [2] "Calcium-binding enhance the activity of the enzyme."                                                                                                      
## [3] "glycerol-3-phosphate dehydrogenase,tightly linked to D2S141,FAD dependent,mitochondrial,intermembrane space predominantly expressed in islet cell"        
## 
## --- RFFL ; BF(dB)= 32.14272 ; M_beta= -0.1062846 
##     Ring Finger And FYVE Like Domain Containing E3 Ubiquitin Protein Ligase 
## [1] "E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. Negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling."
## [2] "Down-regulated upon DNA damage."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
## 
## --- C19ORF43 ; BF(dB)=  ; M_beta=  
##      
## character(0)
## 
## --- ASNA1 ; BF(dB)= 31.98373 ; M_beta= 0.1879322 
##      
## character(0)
## 
## --- KIAA1324 ; BF(dB)= 31.82971 ; M_beta= 0.1682013 
##      
## character(0)
## 
## --- CDH4 ; BF(dB)= 31.82971 ; M_beta= 0.1684987 
##     Cadherin 4 
## [1] "cadherin 4,R-cadherin,transmembrane glycoprotein component of adherens junction,expressed in retina,in brain,involved during brain segmentation and neuronal outgrowth and in kidney"                                                                                         
## [2] "Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. May play an important role in retinal development."
## 
## --- TBC1D19 ; BF(dB)= 31.82971 ; M_beta= 0.1643486 
##     TBC1 Domain Family Member 19 
## [1] "May act as a GTPase-activating protein for Rab family protein(s)."
## 
## --- ELP2 ; BF(dB)= 31.60731 ; M_beta= 0.1324265 
##     Elongator Acetyltransferase Complex Subunit 2 
## [1] "Component of the RNA polymerase II elongator complex, a multiprotein complex associated with the RNA polymerase II (Pol II) holoenzyme, and which is involved in transcriptional elongation (PubMed:11714725, PubMed:11818576). The elongator complex catalyzes formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (PubMed:29332244)."
## 
## --- ZNF618 ; BF(dB)= 31.60731 ; M_beta= 0.1825262 
##     Zinc Finger Protein 618 
## [1] "May be involved in transcriptional regulation."
## 
## --- KIF16B ; BF(dB)= 31.46438 ; M_beta= 0.1187752 
##     Kinesin Family Member 16B 
## [1] "Plus end-directed microtubule-dependent motor protein involved in endosome transport and receptor recycling and degradation. Regulates the plus end motility of early endosomes and the balance between recycling and degradation of receptors such as EGF receptor (EGFR) and FGF receptor (FGFR). Regulates the Golgi to endosome transport of FGFR-containing vesicles during early development, a key process for developing basement membrane and epiblast and primitive endoderm lineages during early postimplantation development."
## 
## --- FNDC3B ; BF(dB)= 31.25736 ; M_beta= -0.1751153 
##     Fibronectin Type III Domain Containing 3B 
## [1] "May be a positive regulator of adipogenesis."
## 
## --- IGSF21 ; BF(dB)= 31.12393 ; M_beta= 0.1048499 
##     Immunoglobin Superfamily Member 21 
## [1] "Involved in synaptic inhibition in the brain. Selectively regulates inhibitory presynaptic differentiation through interacting with presynaptic NRXN2."
## 
## --- SPTB ; BF(dB)= 30.86716 ; M_beta= 0.1829784 
##     Spectrin Beta, Erythrocytic 
## [1] "spectrin,beta,erythrocytic,intermediate filament associated protein (IFAP,type III),dimerizing and heteropolymerizing,components of the core structure of the membrane skeleton"                                            
## [2] "Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane. It associates with band 4.1 and actin to form the cytoskeletal superstructure of the erythrocyte plasma membrane."
## 
## --- MICU3 ; BF(dB)= 30.62268 ; M_beta= 0.1660945 
##     Mitochondrial Calcium Uptake Family Member 3 
## [1] "May play a role in mitochondrial calcium uptake."
## 
## --- GABPA ; BF(dB)= 30.62268 ; M_beta= 0.2037936 
##     GA Binding Protein Transcription Factor Subunit Alpha 
## [1] "GA binding protein,alpha subunit with an ETS related domain,component of the nuclear respiratory factor 2,ubiquitously expressed,interacting with the four ankyrin-type repeats to form a high affinity DNA-binding complex recognizing an important site for herpes simplex virus type I activation,putatively involved in the activation of nuclear genes specifying mitochondrial function"
## [2] "Transcription factor capable of interacting with purine rich repeats (GA repeats). Necessary for the expression of the Adenovirus E4 gene."                                                                                                                                                                                                                                                   
## 
## --- EVC ; BF(dB)= 30.44664 ; M_beta= 0.1599062 
##     EvC Ciliary Complex Subunit 1 
## [1] "Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling. Involved in endochondral growth and skeletal development."
## 
## --- CRMP1 ; BF(dB)= 30.44664 ; M_beta= 0.1599062 
##     Collapsin Response Mediator Protein 1 
## [1] "Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton (PubMed:25358863). Plays a role in axon guidance (PubMed:25358863). During the axon guidance process, acts downstream of SEMA3A to promote FLNA dissociation from F-actin which results in the rearrangement of the actin cytoskeleton and the collapse of the growth cone (PubMed:25358863). Involved in invasive growth and cell migration (PubMed:11562390). May participate in cytokinesis (PubMed:19799413)."
## 
## --- INTS9 ; BF(dB)= 30.44664 ; M_beta= 0.1556117 
##     Integrator Complex Subunit 9 
## [1] "Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes (Probable). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex (PubMed:23904267)."
## 
## --- PIEZO2 ; BF(dB)= 30.44664 ; M_beta= 0.1618019 
##     Piezo Type Mechanosensitive Ion Channel Component 2 
## [1] "Component of a mechanosensitive channel required for rapidly adapting mechanically activated (MA) currents. Required for Merkel-cell mechanotransduction. Plays a major role in light-touch mechanosensation."
## 
## --- ZNF469 ; BF(dB)= 30.22083 ; M_beta= -0.1583689 
##     Zinc Finger Protein 469 
## [1] "May be involved in transcriptional regulation."
## 
## --- CEP89 ; BF(dB)= 30.16587 ; M_beta= 0.09619318 
##     Centrosomal Protein 89 
## [1] "Required for ciliogenesis. Also plays a role in mitochondrial metabolism where it may modulate complex IV activity."
## 
## --- RHPN2 ; BF(dB)= 30.16587 ; M_beta= 0.09619318 
##     Rhophilin Rho GTPase Binding Protein 2 
## [1] "Binds specifically to GTP-Rho. May function in a Rho pathway to limit stress fiber formation and/or increase the turnover of F-actin structures in the absence of high levels of RhoA activity."
## [2] "By thyrotropin (TSH). Regulated by the cAMP pathway."                                                                                                                                           
## 
## --- C1ORF56 ; BF(dB)=  ; M_beta=  
##     Chromosome 1 Open Reading Frame 56 
## [1] "Involved in control of cellular proliferation. Onconcogenic modifier contributing to the tumor suppressor function of DNMT3B."
## 
## --- BNIPL ; BF(dB)= 30.05764 ; M_beta= 0.1867536 
##     BCL2 Interacting Protein Like 
## [1] "May be a bridge molecule between BCL2 and ARHGAP1/CDC42 in promoting cell death."
## 
## --- LYG2 ; BF(dB)= 30.05764 ; M_beta= 0.1817917 
##     Lysozyme G2 
## [1] "May act as a potent antibacterial protein that may play a role in the innate immunity."
## 
## --- AFF3 ; BF(dB)= 30.00434 ; M_beta= 0.1238393 
##     AF4/FMR2 Family Member 3 
## [1] "Putative transcription activator that may function in lymphoid development and oncogenesis. Binds, in vitro, to double-stranded DNA."
## 
## --- SLC9A3 ; BF(dB)= 29.95158 ; M_beta= 0.114778 
##     Solute Carrier Family 9 Member A3 
## [1] "solute carrier protein family 9 (sodium/hydrogen exchange),member 3,involved in intracellular pH regulation and cell volume,isoform 3B,apical epithelium,expressed in kidney,gastrointestinal tract (amiloride insensitive)"                                                   
## [2] "Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient (PubMed:26358773). Plays an important role in signal transduction."
## 
## --- EXOC3 ; BF(dB)= 29.95158 ; M_beta= 0.114778 
##     Exocyst Complex Component 3 
## [1] "Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane."
## 
## --- CD1A ; BF(dB)= 29.95158 29.64551 27.35485 ; M_beta= 0.1294895 0.1357648 0.1388076 
##     CD1a Molecule 
## [1] "cell differentiation antigen CD1A (T6),49kDa,membrane glycoprotein,B2M associated,identified by monoclonal antibodies NA1/34,T6,VIT6,Leu6 (see CD1@)"  
## [2] "Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells."
## 
## --- OTUD7B ; BF(dB)= 29.89933 ; M_beta= 0.1606438 
##     OTU Deubiquitinase 7B 
## [1] "Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses. In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B. Negatively regulates mucosal immunity against infections (By similarity). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (By similarity). Mediates deubiquitination of EGFR (PubMed:22179831). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains (PubMed:27732584). Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure (PubMed:27732584). Hydrolyzes both linear and branched forms of polyubiquitin."
## [2] "By TNF-alpha."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
## [3] "Deubiquitinase activity is inhibited following interaction with PARK7."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
## 
## --- LRP1 ; BF(dB)= 29.8476 ; M_beta= 0.07688883 
##     LDL Receptor Related Protein 1 
## [1] "Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells (PubMed:11907044, PubMed:12713657). Required for early embryonic development (By similarity). Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. Acts as an LRPAP1 alpha-2-macroglobulin receptor (PubMed:26142438, PubMed:1702392). Acts as TAU/MAPT receptor and controls the endocytosis of TAU/MAPT as well as its subsequent spread (PubMed:32296178). May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission (PubMed:12888553)."
## [2] "(Microbial infection) Functions as a receptor for Pseudomonas aeruginosa exotoxin A."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
## [3] "low-density lipoprotein receptor related protein 1,600kDa,LDLR superfamily,putative susceptibility factor for Alzheimer disease"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
## 
## --- HSD17B7 ; BF(dB)= 29.69532 ; M_beta= 0.1643333 
##     Hydroxysteroid 17-Beta Dehydrogenase 7 
## [1] "Bifunctional enzyme involved in steroid-hormone metabolism and cholesterol biosynthesis (PubMed:12574203, PubMed:12732193, PubMed:12829805, PubMed:20659585, PubMed:19772289, PubMed:11165030). Catalyzes the NADP(H)-dependent reduction of estrogens and androgens and regulates the biological potency of these steroids. Converts estrone (E1) to a more potent estrogen, 17beta-estradiol (E2) (PubMed:12574203, PubMed:12732193, PubMed:19772289). Converts dihydrotestosterone (DHT) to its inactive form 5a-androstane-3b,17b-diol (PubMed:12574203, PubMed:12732193, PubMed:19772289). Converts moderately progesterone to 3beta-hydroxypregn-4-ene-20-one, leading to its inactivation (PubMed:12574203, PubMed:12732193). Additionally, participates in the post-squalene cholesterol biosynthesis, as a 3-ketosteroid reductase (PubMed:12829805, PubMed:20659585, PubMed:11165030)."
## [2] "[Isoform 3]: Does not have enzymatic activities toward E1 and DHT."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
## [3] "Estradiol 17-beta-dehydrogenase and dihydrotestosterone oxidoreductase activities are selectively inhibited by 4-methyl-4-aza-5alpha-androstane derivatives, such as 17beta-[(N-Heptyl)methylamino]-4-aza-5r-androstan-3-one and 17beta-(N-Decylformamido)-4-aza-5r-androstan-3-one."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
## [4] "17 beta hydroxysteroid dehydrogenase type 7,expressed in the corpus luteum during pregnancy,responsible for extradive biosynthesis"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
## 
## --- OR51Q1 ; BF(dB)= 29.64551 ; M_beta= 0.1437771 
##     Olfactory Receptor Family 51 Subfamily Q Member 1 
## [1] "Odorant receptor."
## 
## --- HBE1 ; BF(dB)= 29.64551 ; M_beta= 0.1437771 
##     Hemoglobin Subunit Epsilon 1 
## [1] "hemoglobin,epsilon 1,embryonic"                                                 
## [2] "The epsilon chain is a beta-type chain of early mammalian embryonic hemoglobin."
## 
## --- HBG2 ; BF(dB)= 29.64551 ; M_beta= 0.1437771 
##     Hemoglobin Subunit Gamma 2 
## [1] "globin,gamma G,fetal (G 136)"                                                  
## [2] "Gamma chains make up the fetal hemoglobin F, in combination with alpha chains."
## 
## --- ZNF446 ; BF(dB)= 29.64551 ; M_beta= 0.0998018 
##     Zinc Finger Protein 446 
## [1] "May be involved in transcriptional regulation."
## 
## --- ZNF324 ; BF(dB)= 29.64551 ; M_beta= 0.0998018 
##     Zinc Finger Protein 324 
## [1] "May be involved in transcriptional regulation. May be involved in regulation of cell proliferation."                                                      
## [2] "Induced at the early stage of T cell activation. Regulated at the transcriptional level during the cell cycle. Induced at a maximum level in the S phase."
## 
## --- HAVCR1 ; BF(dB)= 29.54725 ; M_beta= 0.1027923 
##     Hepatitis A Virus Cellular Receptor 1 
## [1] "May play a role in T-helper cell development and the regulation of asthma and allergic diseases. Receptor for TIMD4 (By similarity). May play a role in kidney injury and repair."                                                                                                  
## [2] "(Microbial infection) Acts as a receptor for Hepatitis A virus."                                                                                                                                                                                                                    
## [3] "(Microbial infection) Acts as a receptor for Ebolavirus and Marburg virus by binding exposed phosphatidyl-serine at the surface of virion membrane (PubMed:21536871). Serves as a dual receptor for Ebolavirus by also interacting with envelope glycoprotein GP (PubMed:26487564)."
## [4] "(Microbial infection) Acts as a receptor for Dengue virus by binding exposed phosphatidyl-serine at the surface of virion membrane."                                                                                                                                                
## [5] "(Microbial infection) Acts as a receptor for Zika virus by binding to envelope protein E."                                                                                                                                                                                          
## [6] "Up-regulated in the kidney in renal diseases (at protein level)."                                                                                                                                                                                                                   
## 
## --- CNPY2 ; BF(dB)= 29.49878 ; M_beta= 0.08950031 
##     Canopy FGF Signaling Regulator 2 
## [1] "Positive regulator of neurite outgrowth by stabilizing myosin regulatory light chain (MRLC). It prevents MIR-mediated MRLC ubiquitination and its subsequent proteasomal degradation."
## 
## --- PIK3C2G ; BF(dB)= 29.49878 ; M_beta= 0.1202544 
##     Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Gamma 
## [1] "phosphatidylinositol 3-kinase class 2,gamma polypeptide,expressed in normal breast,liver,prostate and other tissues"                                                                                           
## [2] "Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. May play a role in SDF1A-stimulated chemotaxis (By similarity)."
## 
## --- COPS4 ; BF(dB)= 29.40311 ; M_beta= 0.1858362 
##     COP9 Signalosome Subunit 4 
## [1] "Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. Also involved in the deneddylation of non-cullin subunits such as STON2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1, IRF8/ICSBP and SNAPIN, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively."
## 
## --- EHD2 ; BF(dB)= 29.08086 ; M_beta= 0.08337958 
##     EH Domain Containing 2 
## [1] "ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis (By similarity). Plays a role in membrane trafficking between the plasma membrane and endosomes (PubMed:17233914). Important for the internalization of GLUT4. Required for fusion of myoblasts to skeletal muscle myotubes. Required for normal translocation of FER1L5 to the plasma membrane (By similarity). Regulates the equilibrium between cell surface-associated and cell surface-dissociated caveolae by constraining caveolae at the cell membrane (PubMed:25588833)."
## [2] "The very low intrinsic ATPase activity is increased upon interaction with liposomes."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
## 
## --- LRIG1 ; BF(dB)= 29.03633 ; M_beta= -0.1908335 
##     Leucine Rich Repeats And Immunoglobulin Like Domains 1 
## [1] "Acts as a feedback negative regulator of signaling by receptor tyrosine kinases, through a mechanism that involves enhancement of receptor ubiquitination and accelerated intracellular degradation."
## [2] "By EGF."                                                                                                                                                                                             
## 
## --- SLC25A26 ; BF(dB)= 29.03633 ; M_beta= -0.1908335 
##     Solute Carrier Family 25 Member 26 
## [1] "Mitochondrial solute carriers shuttle metabolites, nucleotides, and cofactors through the mitochondrial inner membrane. Specifically mediates the transport of S-adenosylmethionine (SAM) into the mitochondria."
## [2] "Strongly inhibited by tannic acid and Bromocresol Purple."                                                                                                                                                       
## 
## --- HSPA5 ; BF(dB)= 28.69222 ; M_beta= 0.195582 
##     Heat Shock Protein Family A (Hsp70) Member 5 
## [1] "Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (PubMed:2294010, PubMed:23769672, PubMed:23990668, PubMed:28332555). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR) (PubMed:1550958, PubMed:19538957). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1 (By similarity). Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. May also play a role in apoptosis and cell proliferation (PubMed:26045166)."
## [2] "(Microbial infection) Plays an important role in viral binding to the host cell membrane and entry for several flaviruses such as Dengue virus, Zika virus and Japanese encephalitis virus (PubMed:33432092, PubMed:15098107, PubMed:28053106). Acts as a component of the cellular receptor for Dengue virus serotype 2/DENV-2 on human liver cells (PubMed:15098107)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
## [3] "By endoplasmic reticulum stress."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
## [4] "The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains. In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction (PubMed:26655470). In contrast, in the ATP-bound state the two domains are tightly coupled, which results in drastically accelerated kinetics in both binding and release of polypeptide substrates (PubMed:26655470). J domain-containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP (By similarity). Homooligomerization inactivates participating HSPA5/BiP protomers and probably act as reservoirs to store HSPA5/BiP molecules when they are not needed by the cell (By similarity)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
## [5] "glucose regulated protein (78kDa),HSP70 homolog,in the endoplasmic reticulum,subunit of PPP1CC2"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
## 
## --- PODXL ; BF(dB)= 28.4873 ; M_beta= 0.1543472 
##     Podocalyxin Like 
## [1] "Involved in the regulation of both adhesion and cell morphology and cancer progression. Functions as an anti-adhesive molecule that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion. Acts as a pro-adhesive molecule, enhancing the adherence of cells to immobilized ligands, increasing the rate of migration and cell-cell contacts in an integrin-dependent manner. Induces the formation of apical actin-dependent microvilli. Involved in the formation of a preapical plasma membrane subdomain to set up initial epithelial polarization and the apical lumen formation during renal tubulogenesis. Plays a role in cancer development and aggressiveness by inducing cell migration and invasion through its interaction with the actin-binding protein EZR. Affects EZR-dependent signaling events, leading to increased activities of the MAPK and PI3K pathways in cancer cells."
## [2] "podocalyxin-like protein,integral component of the glomerular epithelial cell glycocalyx"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
## 
## --- KRT73 ; BF(dB)= 28.4873 ; M_beta= 0.08404193 
##     Keratin 73 
## [1] "Has a role in hair formation. Specific component of keratin intermediate filaments in the inner root sheath (IRS) of the hair follicle (Probable)."
## 
## --- ZNF878 ; BF(dB)= 28.25064 ; M_beta= 0.1201999 
##     Zinc Finger Protein 878 
## [1] "May be involved in transcriptional regulation."
## 
## --- SH3RF3 ; BF(dB)= 28.02318 ; M_beta= 0.09169092 
##     SH3 Domain Containing Ring Finger 3 
## [1] "Has E3 ubiquitin-protein ligase activity."
## 
## --- SAMD11 ; BF(dB)= 27.87624 ; M_beta= 0.1537605 
##     Sterile Alpha Motif Domain Containing 11 
## [1] "May play a role in photoreceptor development."
## 
## --- NOC2L ; BF(dB)= 27.87624 ; M_beta= 0.1537605 
##     NOC2 Like Nucleolar Associated Transcriptional Repressor 
## [1] "Acts as an inhibitor of histone acetyltransferase activity; prevents acetylation of all core histones by the EP300/p300 histone acetyltransferase at p53/TP53-regulated target promoters in a histone deacetylases (HDAC)-independent manner. Acts as a transcription corepressor of p53/TP53- and TP63-mediated transactivation of the p21/CDKN1A promoter. Involved in the regulation of p53/TP53-dependent apoptosis. Associates together with TP63 isoform TA*-gamma to the p21/CDKN1A promoter."
## [2] "Up-regulated by IL4 and CD40L in B-cells."                                                                                                                                                                                                                                                                                                                                                                                                                                                           
## 
## --- LRRTM3 ; BF(dB)= 27.6274 ; M_beta= 0.05394449 
##     Leucine Rich Repeat Transmembrane Neuronal 3 
## [1] "Exhibits a limited synaptogenic activity in vitro, restricted to excitatory presynaptic differentiation (By similarity). May play a role in the development and maintenance of the vertebrate nervous system."
## 
## --- CTNNA3 ; BF(dB)= 27.6274 ; M_beta= 0.05394449 
##     Catenin Alpha 3 
## [1] "May be involved in formation of stretch-resistant cell-cell adhesion complexes."
## 
## --- SWAP70 ; BF(dB)= 27.6274 ; M_beta= 0.146106 
##     Switching B Cell Complex Subunit SWAP70 
## [1] "Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which, independently of RAS, transduces signals from tyrosine kinase receptors to RAC. It also mediates signaling of membrane ruffling. Regulates the actin cytoskeleton as an effector or adapter protein in response to agonist stimulated phosphatidylinositol (3,4)-bisphosphate production and cell protrusion (By similarity)."
## 
## --- MMP26 ; BF(dB)= 27.35485 ; M_beta= 0.1519582 
##     Matrix Metallopeptidase 26 
## [1] "May hydrolyze collagen type IV, fibronectin, fibrinogen, beta-casein, type I gelatin and alpha-1 proteinase inhibitor. Is also able to activate progelatinase B."
## 
## --- DENND3 ; BF(dB)= 27.35485 ; M_beta= 0.1173389 
##     DENN Domain Containing 3 
## [1] "Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form (PubMed:20937701). Regulates autophagy in response to starvation through RAB12 activation. Starvation leads to ULK1/2-dependent phosphorylation of Ser-472 and Ser-490, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards RAB12 (By similarity). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:20937701). Starvation also induces phosphorylation at Tyr-858, which leads to up-regulated GEF activity and initiates autophagy (By similarity)."
## 
## --- TTC3 ; BF(dB)= 27.3216 ; M_beta= 0.1063328 
##     Tetratricopeptide Repeat Domain 3 
## [1] "tetratricopeptide-repeat containing gene isoform 3,on the Down syndrome critical region,predominantly expressed in the central nervous system"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
## [2] "E3 ubiquitin-protein ligase which catalyzes the formation of 'Lys-48'-polyubiquitin chains (PubMed:20059950, PubMed:30696809). Mediates the ubiquitination and subsequent degradation of phosphorylated Akt (AKT1, AKT2 and AKT3) in the nucleus (PubMed:20059950). Acts as a terminal regulator of Akt signaling after activation; its phosphorylation by Akt, which is a prerequisite for ubiquitin ligase activity, suggests the existence of a regulation mechanism required to control Akt levels after activation (PubMed:20059950). Positively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation by mediating the ubiquitination and subsequent degradation of SMURF2 (PubMed:30696809). Regulates neuronal differentiation by regulating actin remodeling and Golgi organization via a signaling cascade involving RHOA, CIT and ROCK (PubMed:17488780, PubMed:24695496). Inhibits cell proliferation (PubMed:30203323)."
## [3] "Up-regulated by TGFB1 signaling."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
## 
## --- BSG ; BF(dB)= 27.3216 ; M_beta= 0.06517615 
##     Basigin (Ok Blood Group) 
##  [1] "[Isoform 1]: Essential for normal retinal maturation and development (By similarity). Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photoreceptors (PubMed:25957687). In association with glucose transporter SLC16A1/GLUT1 and NXNL1, promotes retinal cone survival by enhancing aerobic glycolysis and accelerating the entry of glucose into photoreceptors (PubMed:25957687). May act as a potent stimulator of IL6 secretion in multiple cell lines that include monocytes (PubMed:21620857)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
##  [2] "[Isoform 2]: Signaling receptor for cyclophilins, essential for PPIA/CYPA and PPIB/CYPB-dependent signaling related to chemotaxis and adhesion of immune cells (PubMed:11943775, PubMed:11688976). Plays an important role in targeting monocarboxylate transporters SLC16A1/GLUT1, SLC16A11 and SLC16A12 to the plasma membrane (PubMed:17127621, PubMed:21778275, PubMed:28666119). Acts as a coreceptor for vascular endothelial growth factor receptor 2 (KDR/VEGFR2) in endothelial cells enhancing its VEGFA-mediated activation and downstream signaling (PubMed:25825981). Promotes angiogenesis through EPAS1/HIF2A-mediated up-regulation of VEGFA (isoform VEGF-165 and VEGF-121) and KDR/VEGFR2 in endothelial cells (PubMed:19837976). Plays a key role in regulating tumor growth, invasion, metastasis and neoangiogenesis by stimulating the production and release of extracellular matrix metalloproteinases and KDR/VEGFR2 by both tumor cells and stromal cells (fibroblasts and endothelial cells) (PubMed:12553375, PubMed:11992541, PubMed:15833850)."
##  [3] "[Isoform 1]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7 and Dd2."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
##  [4] "[Isoform 2]: (Microbial infection) Erythrocyte receptor for P.falciparum RH5 which is essential for erythrocyte invasion by the merozoite stage of P.falciparum isolates 3D7, Dd2, 7G8 and HB3 (PubMed:22080952, PubMed:26195724). Binding of P.falciparum RH5 results in BSG dimerization which triggers an increase in intracellular Ca(2+) in the erythrocyte (PubMed:28409866). This essential step leads to a rearrangement of the erythrocyte cytoskeleton required for the merozoite invasion (PubMed:28409866)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
##  [5] "[Isoform 2]: (Microbial infection) Can facilitate human SARS coronavirus (SARS-CoV-1) infection via its interaction with virus-associated PPIA/CYPA."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
##  [6] "[Isoform 2]: (Microbial infection) Can facilitate HIV-1 infection via its interaction with virus-associated PPIA/CYPA."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
##  [7] "[Isoform 2]: (Microbial infection) First described as a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is not required for SARS-CoV-2 infection."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
##  [8] "[Isoform 2]: (Microbial infection) Acts as a receptor for measles virus."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
##  [9] "[Isoform 2]: (Microbial infection) Promotes entry of pentamer-expressing human cytomegalovirus (HCMV) into epithelial and endothelial cells."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
## [10] "basigin,widely expressed,involved in cell recognition,broadly expressed on hematopoietic cells stimulating nearly fibroblasts to synthesize matrix metalloproteinases,member of the Ig superfamily"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
## 
## --- FICD ; BF(dB)= 27.28853 ; M_beta= -0.1639816 
##     FIC Domain Protein Adenylyltransferase 
## [1] "Protein that can both mediate the addition of adenosine 5'-monophosphate (AMP) to specific residues of target proteins (AMPylation), and the removal of the same modification from target proteins (de-AMPylation), depending on the context (By similarity). The side chain of Glu-231 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place (By similarity). Acts as a key regulator of the ERN1/IRE1-mediated unfolded protein response (UPR) by mediating AMPylation or de-AMPylation of HSPA5/BiP (PubMed:25601083). In unstressed cells, acts as an adenylyltransferase by mediating AMPylation of HSPA5/BiP at 'Thr-518', thereby inactivating it (By similarity). In response to endoplasmic reticulum stress, acts as a phosphodiesterase by mediating removal of ATP (de-AMPylation) from HSPA5/BiP at 'Thr-518', leading to restore HSPA5/BiP activity (By similarity). Although it is able to AMPylate RhoA, Rac and Cdc42 Rho GTPases in vitro, Rho GTPases do not constitute physiological substrates (PubMed:19362538, PubMed:25601083)."
## [2] "Up-regulated in response to activation of unfolded protein response (UPR)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
## [3] "The side chain of Glu-234 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-234 binds ATP and competes with ATP-binding at Arg-374, thereby preventing adenylyltransferase activity (PubMed:22266942, PubMed:25435325). In unstressed cells, disengagement of Glu-234 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-234, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (PubMed:22266942, PubMed:25435325)."                                                                                                                                                                                                                                                               
## 
## --- SLAMF6 ; BF(dB)= 27.25563 ; M_beta= 0.164416 
##     SLAM Family Member 6 
## [1] "Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Triggers cytolytic activity only in natural killer cells (NK) expressing high surface densities of natural cytotoxicity receptors (PubMed:11489943, PubMed:16920955). Positive signaling in NK cells implicates phosphorylation of VAV1. NK cell activation seems to depend on SH2D1B and not on SH2D1A (PubMed:16920955). In conjunction with SLAMF1 controls the transition between positive selection and the subsequent expansion and differentiation of the thymocytic natural killer T (NKT) cell lineage (By similarity). Promotes T-cell differentiation into a helper T-cell Th17 phenotype leading to increased IL-17 secretion; the costimulatory activity requires SH2D1A (PubMed:22184727, PubMed:16920955). Promotes recruitment of RORC to the IL-17 promoter (PubMed:22989874). In conjunction with SLAMF1 and CD84/SLAMF5 may be a negative regulator of the humoral immune response. In the absence of SH2D1A/SAP can transmit negative signals to CD4(+) T-cells and NKT cells. Negatively regulates germinal center formation by inhibiting T-cell:B-cell adhesion; the function probably implicates increased association with PTPN6/SHP-1 via ITSMs in absence of SH2D1A/SAP. However, reported to be involved in maintaining B-cell tolerance in germinal centers and in preventing autoimmunity (By similarity)."
## 
## --- RALGDS ; BF(dB)= 27.25563 ; M_beta= 0.1716983 
##     Ral Guanine Nucleotide Dissociation Stimulator 
## [1] "Stimulates the dissociation of GDP from the Ras-related RalA and RalB GTPases which allows GTP binding and activation of the GTPases. Interacts and acts as an effector molecule for R-Ras, H-Ras, K-Ras, and Rap."
## [2] "Ral guanine nucleotide dissociation stimulator,related protein,115kDa,involved in signal transduction"                                                                                                             
## 
## --- NGRN ; BF(dB)= 27.25563 ; M_beta= 0.111169 
##     Neugrin, Neurite Outgrowth Associated 
## [1] "Plays an essential role in mitochondrial ribosome biogenesis. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation of core subunits of the oxidative phosphorylation system."
## [2] "Highly up-regulated in neuroblastostoma cells by retinoic acid treatment inducing neurite outgrowth."                                                                                                                                                                                                                                                                      
## 
## --- B4GALNT1 ; BF(dB)= 27.12571 ; M_beta= 0.07911236 
##     Beta-1,4-N-Acetyl-Galactosaminyltransferase 1 
## [1] "Involved in the biosynthesis of gangliosides GM2, GD2, GT2 and GA2 from GM3, GD3, GT3 and GA3, respectively."
## 
## --- EEF1D ; BF(dB)= 26.99838 ; M_beta= 0.1065659 
##     Eukaryotic Translation Elongation Factor 1 Delta 
## [1] "eukaryotic translation elongation factor 1,delta"                                                                                                                                            
## [2] "[Isoform 1]: EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP, regenerating EF-1-alpha for another round of transfer of aminoacyl-tRNAs to the ribosome."   
## [3] "[Isoform 2]: Regulates induction of heat-shock-responsive genes through association with heat shock transcription factors and direct DNA-binding at heat shock promoter elements (HSE)."     
## [4] "By homocysteine (HC), may mediate accelerated synthesis of free thiol-containing proteins in response to HC-induced oxidative stress. Also induced following exposure to ionizing radiation."
## 
## --- SLAMF8 ; BF(dB)= 26.39621 ; M_beta= 0.1354282 
##     SLAM Family Member 8 
## [1] "May play a role in B-lineage commitment and/or modulation of signaling through the B-cell receptor."
## 
## --- HSPBP1 ; BF(dB)= 26.25367 ; M_beta= 0.1573973 
##     HSPA (Hsp70) Binding Protein 1 
## [1] "Inhibits HSPA1A chaperone activity by changing the conformation of the ATP-binding domain of HSPA1A and interfering with ATP binding. Interferes with ubiquitination mediated by STUB1 and inhibits chaperone-assisted degradation of immature CFTR."
## 
## --- ESRRB ; BF(dB)= 26.00415 ; M_beta= 0.06786162 
##     Estrogen Related Receptor Beta 
## [1] "[Isoform 3]: Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity (PubMed:17920186, PubMed:19755138). Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways. Upon FGF signaling pathway activation, interacts with KDM1A by directly binding to enhancer site of ELF5 and EOMES and activating their transcription leading to self-renewal of trophoblast stem cells. Also regulates expression of multiple rod-specific genes and is required for survival of this cell type (By similarity). Plays a role as transcription factor activator of GATA6, NR0B1, POU5F1 and PERM1 (PubMed:23836911). Plays a role as transcription factor repressor of NFE2L2 transcriptional activity and ESR1 transcriptional activity (PubMed:17920186, PubMed:19755138). During mitosis remains bound to a subset of interphase target genes, including pluripotency regulators, through the canonical ESRRB recognition (ERRE) sequence, leading to their transcriptional activation in early G1 phase. Can coassemble on structured DNA elements with other transcription factors like SOX2, POU5F1, KDM1A and NCOA3 to trigger ESRRB-dependent gene activation. This mechanism, in the case of SOX2 corecruitment prevents the embryonic stem cells (ESCs) to epiblast stem cells (EpiSC) transition through positive regulation of NR0B1 that inhibits the EpiSC transcriptional program. Also plays a role inner ear development by controlling expression of ion channels and transporters and in early placentation (By similarity)."
## [2] "[Isoform 1]: Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity. Positively regulates ESR1 transcriptional activity upon E2 stimulation."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
## [3] "estrogen-related receptor B,widely expressed,orphan receptor family,steroid/thyroid hormone receptor superfamily,repressing glucocorticoid receptor activity in a cell specific fashion"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
## 
## --- ZNHIT1 ; BF(dB)= 25.94986 ; M_beta= -0.06337368 
##     Zinc Finger HIT-Type Containing 1 
## [1] "Seems to play a role in p53-mediated apoptosis induction (PubMed:17380123). Binds to NR1D2 and relieves it of its inhibitory effect on the transcription of APOC3 without affecting its DNA-binding activity (PubMed:17892483)."
## [2] "Induced by DNA damage."                                                                                                                                                                                                         
## 
## --- STAT5A ; BF(dB)= 25.92287 ; M_beta= -0.1772424 
##     Signal Transducer And Activator Of Transcription 5A 
## [1] "signal transducer and activator of transcription 5A of the GH JAK/STAT pathway,constitutively expressed in peripheral blood lymphocytes,activated by a variety of hormones and cytokines including interleukin 2,interacting with T cell receptor and stimulating T cell proliferation"                                                                                                                          
## [2] "Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Mediates cellular responses to ERBB4. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the GAS element and activates PRL-induced transcription. Regulates the expression of milk proteins during lactation."
## 
## --- GPR39 ; BF(dB)= 25.6843 ; M_beta= 0.1125904 
##     G Protein-Coupled Receptor 39 
## [1] "G protein coupled receptor 39,with two forms generated by alternative polyadenylation sites,highly homolog to growth hormone,secretagogue receptor (GSHR) and neurotensin receptors,expressed in the brain and other tissues"                                                                                                                                    
## [2] "Zn(2+) acts as an agonist. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated mainly through G(q)-alpha and G(12)/G(13) proteins. Involved in regulation of body weight, gastrointestinal mobility, hormone secretion and cell death (By similarity)."
## 
## --- TMEM74B ; BF(dB)= 25.58066 ; M_beta= -0.1595426 
##      
## character(0)
## 
## --- PSMF1 ; BF(dB)= 25.58066 ; M_beta= -0.1595426 
##     Proteasome Inhibitor Subunit 1 
## [1] "Plays an important role in control of proteasome function. Inhibits the hydrolysis of protein and peptide substrates by the 20S proteasome. Also inhibits the activation of the proteasome by the proteasome regulatory proteins PA700 and PA28."
## 
## --- TOM1L2 ; BF(dB)= 25.55498 ; M_beta= 0.1092485 
##     Target Of Myb1 Like 2 Membrane Trafficking Protein 
## [1] "Probable role in protein transport. May regulate growth factor-induced mitogenic signaling."                                        
## [2] "v-Myb target gene-like 2,retroviral oncogene,involved in transformation of myelomonoctic cells,in the Smith-Magenis critical region"
## 
## --- all  missing genes
## [1] "TSPAN18"  "SLC22A10" "SLC22A25" "C19ORF43" "ASNA1"    "KIAA1324" "TMEM74B" 
## 
## 
## 
## 
## - ce 
## -- f_over_sum_known_trees 
## --- PCP2 ; BF(dB)= 52.96448 ; M_beta= 0.2021141 
##     Purkinje Cell Protein 2 
## [1] "May function as a cell-type specific modulator for G protein-mediated cell signaling."
## 
## --- PET100 ; BF(dB)= 52.96448 42.1487 ; M_beta= 0.2021141 0.2382433 
##     PET100 Cytochrome C Oxidase Chaperone 
## [1] "Plays an essential role in mitochondrial complex IV maturation and assembly."
## 
## --- XAB2 ; BF(dB)= 52.96448 42.1487 ; M_beta= 0.2021141 0.2382433 
##     XPA Binding Protein 2 
## [1] "Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28502770, PubMed:28076346). Involved in transcription-coupled repair (TCR), transcription and pre-mRNA splicing (PubMed:10944529, PubMed:17981804)."
## 
## --- DOCK5 ; BF(dB)= 52.96448 ; M_beta= 0.1454179 
##     Dedicator Of Cytokinesis 5 
## [1] "Guanine nucleotide exchange factor (GEF) for Rho and Rac. GEF proteins activate small GTPases by exchanging bound GDP for free GTP (By similarity). Along with DOCK1, mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen (PubMed:19004829)."
## 
## --- DZIP1 ; BF(dB)= 49.95201 ; M_beta= -0.1946517 
##     DAZ Interacting Zinc Finger Protein 1 
## [1] "May participate in spermatogenesis via its interaction with DAZ1 (PubMed:15081113). Has a role in primary cilium formation (PubMed:19852954)."
## 
## --- WDR19 ; BF(dB)= 49.95201 ; M_beta= -0.2628328 
##     WD Repeat Domain 19 
## [1] "As component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in cilia function and/or assembly (PubMed:20889716). Essential for functional IFT-A assembly and ciliary entry of GPCRs (PubMed:20889716). Associates with the BBSome complex to mediate ciliary transport (By similarity)."
## [2] "By androgenic hormones. Expression increased 3-fold in an androgen-stimulated androgen-sensitive prostate adenocarcinoma cell line compared with androgen-deprived cells."                                                                                                                                                                                                                             
## 
## --- ZCCHC9 ; BF(dB)= 49.95201 ; M_beta= 0.2258253 
##     Zinc Finger CCHC-Type Containing 9 
## [1] "May down-regulate transcription mediated by NF-kappa-B and the serum response element."
## 
## --- ASPH ; BF(dB)= 49.95201 ; M_beta= 0.233851 
##     Aspartate Beta-Hydroxylase 
## [1] "[Isoform 1]: specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins."                                                                              
## [2] "[Isoform 8]: membrane-bound Ca(2+)-sensing protein, which is a structural component of the ER-plasma membrane junctions. Isoform 8 regulates the activity of Ca(+2) released-activated Ca(+2) (CRAC) channels in T-cells."
## 
## --- MOGAT1 ; BF(dB)= 49.95201 ; M_beta= -0.2493903 
##     Monoacylglycerol O-Acyltransferase 1 
## [1] "Catalyzes the formation of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA. Probably not involved in absorption of dietary fat in the small intestine."
## 
## --- SLC6A7 ; BF(dB)= 49.95201 ; M_beta= 0.2301506 
##     Solute Carrier Family 6 Member 7 
## [1] "Terminates the action of proline by its high affinity sodium-dependent reuptake into presynaptic terminals."
## 
## --- ADAMTS17 ; BF(dB)= 49.95201 ; M_beta= -0.2340252 
##     ADAM Metallopeptidase With Thrombospondin Type 1 Motif 17 
## character(0)
## 
## --- ABHD17A ; BF(dB)= 49.95201 ; M_beta= 0.2098657 
##     Abhydrolase Domain Containing 17A, Depalmitoylase 
## [1] "Hydrolyzes fatty acids from S-acylated cysteine residues in proteins (PubMed:26701913). Has depalmitoylating activity towards NRAS (PubMed:26701913). Has depalmitoylating activity towards DLG4/PSD95 (PubMed:26701913). May have depalmitoylating activity towards MAP6 (By similarity)."
## [2] "Inhibited by palmostatin-B."                                                                                                                                                                                                                                                               
## 
## --- SPDYA ; BF(dB)= 46.93736 ; M_beta= -0.2349687 
##     Speedy/RINGO Cell Cycle Regulator Family Member A 
## [1] "Regulates the G1/S phase transition of the cell cycle by binding and activating CDK1 and CDK2 (PubMed:12972555). Contributes to CDK2 activation without promoting CDK2 phosphorylation, by inducing a conformation change of the CDK2 T-loop that obstructs the substrate-binding cleft prior to kinase activation (PubMed:28666995). Mediates cell survival during the DNA damage process through activation of CDK2 (PubMed:12839962)."
## 
## --- PPP1CB ; BF(dB)= 46.93736 ; M_beta= -0.2349687 
##     Protein Phosphatase 1 Catalytic Subunit Beta 
## [1] "serine/threonine protein phosphatase 1,catalytic subunit,beta"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
## [2] "Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase (PP1) is essential for cell division, it participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208)."
## [3] "Up-regulated in synovial fluid mononuclear cells and peripheral blood mononuclear cells from patients with rheumatoid arthritis."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
## [4] "Inhibited by the toxins okadaic acid, tautomycin and microcystin Leu-Arg (By similarity). The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
## 
## --- DYSF ; BF(dB)= 46.93736 ; M_beta= 0.1884377 
##     Dysferlin 
## [1] "Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress (By similarity)."
## [2] "dysferlin,related to the C elegans spermatogenesis factor fer-1,sarcolemmal protein,highly expressed in skeletal muscle,also expressed in heart and placenta,deleted in SJL mice"                                                                                                     
## 
## --- SLC19A1 ; BF(dB)= 46.93736 ; M_beta= 0.2357639 
##     Solute Carrier Family 19 Member 1 
## [1] "solute carrier family 19,member A1,folate transporter,expressed in placenta,testis,with two alternative non coding exons"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
## [2] "Transporter that mediates the import of reduced folates and a subset of cyclic dinucleotides (PubMed:7826387, PubMed:9041240, PubMed:10787414, PubMed:15337749, PubMed:16115875, PubMed:31126740, PubMed:31511694). Has high affinity for N5-methyltetrahydrofolate, the predominant circulating form of folate (PubMed:10787414, PubMed:14609557, PubMed:22554803). Also able to mediate the import of antifolate drug methotrexate (PubMed:7615551, PubMed:7641195, PubMed:9767079, PubMed:22554803). Acts as an importer of immunoreactive cyclic dinucleotides, such as cyclic GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol, and its linkage isomer 3'-3'-cGAMP (PubMed:31126740, PubMed:31511694). Mechanistically, acts as an antiporter, which export of intracellular organic anions to facilitate uptake of its substrates (PubMed:22554803, PubMed:31126740, PubMed:31511694). 5-amino-4-imidazolecarboxamide riboside (AICAR), when phosphorylated to AICAR monophosphate, can serve as an organic anion for antiporter activity (PubMed:22554803)."
## 
## --- COL18A1 ; BF(dB)= 46.93736 40.89057 ; M_beta= 0.2357639 -0.2260416 
##     Collagen Type XVIII Alpha 1 Chain 
## [1] "Probably plays a major role in determining the retinal structure as well as in the closure of the neural tube."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
## [2] "[Non-collagenous domain 1]: May regulate extracellular matrix-dependent motility and morphogenesis of endothelial and non-endothelial cells; the function requires homotrimerization and implicates MAPK signaling."                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
## [3] "[Endostatin]: Potently inhibits endothelial cell proliferation and angiogenesis (PubMed:9459295). May inhibit angiogenesis by binding to the heparan sulfate proteoglycans involved in growth factor signaling (By similarity). Inhibits VEGFA-induced endothelial cell proliferation and migration. Seems to inhibit VEGFA-mediated signaling by blocking the interaction of VEGFA to its receptor KDR/VEGFR2. Modulates endothelial cell migration in an integrin-dependent manner implicating integrin ITGA5:ITGB1 and to a lesser extent ITGAV:ITGB3 and ITGAV:ITGB5 (By similarity). May negatively regulate the activity of homotrimeric non-collagenous domain 1 (PubMed:11257123)."
## [4] "collagen,type XVIII,alpha 1,multiplexin family with interrupted helical domain"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
## 
## --- OR6F1 ; BF(dB)= 46.93736 ; M_beta= -0.2408896 
##     Olfactory Receptor Family 6 Subfamily F Member 1 
## [1] "Odorant receptor."
## 
## --- SDK1 ; BF(dB)= 46.93736 ; M_beta= -0.2422713 
##     Sidekick Cell Adhesion Molecule 1 
## [1] "Adhesion molecule that promotes lamina-specific synaptic connections in the retina. Expressed in specific subsets of interneurons and retinal ganglion cells (RGCs) and promotes synaptic connectivity via homophilic interactions."
## 
## --- SLC2A9 ; BF(dB)= 46.93736 ; M_beta= -0.216599 
##     Solute Carrier Family 2 Member 9 
## [1] "Urate transporter, which may play a role in the urate reabsorption by proximal tubules (PubMed:18327257, PubMed:28083649). Does not transport glucose, fructose or galactose (PubMed:28083649)."
## 
## --- RDH16 ; BF(dB)= 45.17209 ; M_beta= 0.1846628 
##     Retinol Dehydrogenase 16 
## [1] "Oxidoreductase with a preference for NAD. Oxidizes all-trans-retinol, 9-cis-retinol, 11-cis-retinol and 13-cis-retinol to the corresponding aldehydes (PubMed:10329026, PubMed:12534290, PubMed:9677409). Has higher activity towards CRBP-bound retinol than with free retinol (PubMed:12534290). Oxidizes also 3-alpha-hydroxysteroids. Oxidizes androstanediol and androsterone to dihydrotestosterone and androstanedione. Can also catalyze the reverse reaction (PubMed:10329026, PubMed:9677409, PubMed:29541409)."
## [2] "Transiently up-regulated by retinoic acid."                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
## [3] "Inhibited by citral, perillyl alcohol, geraniol, farnesol and geranyl geraniol."                                                                                                                                                                                                                                                                                                                                                                                                                                          
## 
## --- NMT1 ; BF(dB)= 45.17209 ; M_beta= -0.2396311 
##     N-Myristoyltransferase 1 
## [1] "Adds a myristoyl group to the N-terminal glycine residue of certain cellular and viral proteins."
## 
## --- CSF1R ; BF(dB)= 45.17209 ; M_beta= 0.2090435 
##     Colony Stimulating Factor 1 Receptor 
## [1] "colony-stimulating factor 1 (macrophage),receptor"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
## [2] "Tyrosine-protein kinase that acts as cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding, including the ERK1/2 and the JNK pathway (PubMed:20504948, PubMed:30982609). Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP-1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor. In the central nervous system, may play a role in the development of microglia macrophages (PubMed:30982608)."
## [3] "Up-regulated by glucocorticoids."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
## [4] "Present in an inactive conformation in the absence of bound ligand. CSF1 or IL34 binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib/STI-571 (Gleevec), dasatinib, sunitinib/SU11248, lestaurtinib/CEP-701, midostaurin/PKC-412, Ki20227, linifanib/ABT-869, Axitinib/AG013736, sorafenib/BAY 43-9006 and GW2580."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
## 
## --- COBL ; BF(dB)= 45.17209 ; M_beta= -0.228564 
##     Cordon-Bleu WH2 Repeat Protein 
## [1] "Plays an important role in the reorganization of the actin cytoskeleton. Regulates neuron morphogenesis and increases branching of axons and dendrites. Regulates dendrite branching in Purkinje cells (By similarity). Binds to and sequesters actin monomers (G actin). Nucleates actin polymerization by assembling three actin monomers in cross-filament orientation and thereby promotes growth of actin filaments at the barbed end. Can also mediate actin depolymerization at barbed ends and severing of actin filaments. Promotes formation of cell ruffles."
## 
## --- TFAP4 ; BF(dB)= 45.17209 ; M_beta= 0.235461 
##     Transcription Factor AP-4 
## [1] "Transcription factor that activates both viral and cellular genes by binding to the symmetrical DNA sequence 5'-CAGCTG-3'."           
## [2] "transcription factor AP-4,activating enhancer binding protein 4,involved in signal-mediated trafficking of integral membrane proteins"
## 
## --- FMNL1 ; BF(dB)= 45.17209 ; M_beta= -0.2335578 
##     Formin Like 1 
## [1] "May play a role in the control of cell motility and survival of macrophages (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics and cell shape."
## 
## --- FAM83D ; BF(dB)= 45.17209 ; M_beta= -0.2264513 
##     Family With Sequence Similarity 83 Member D 
## [1] "Probable proto-oncogene that regulates cell proliferation, growth, migration and epithelial to mesenchymal transition. Through the degradation of FBXW7, may act indirectly on the expression and downstream signaling of MTOR, JUN and MYC (PubMed:24344117). May play also a role in cell proliferation through activation of the ERK1/ERK2 signaling cascade (PubMed:25646692). May also be important for proper chromosome congression and alignment during mitosis through its interaction with KIF22."
## [2] "Up-regulated during mitosis."                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
## 
## --- DSE ; BF(dB)= 45.17209 ; M_beta= 0.2014172 
##     Dermatan Sulfate Epimerase 
## [1] "Converts D-glucuronic acid to L-iduronic acid (IdoUA) residues. Plays an important role in the biosynthesis of the glycosaminoglycan/mucopolysaccharide dermatan sulfate."
## 
## --- RASAL2 ; BF(dB)= 43.91835 ; M_beta= 0.2526685 
##     RAS Protein Activator Like 2 
## [1] "Inhibitory regulator of the Ras-cyclic AMP pathway."
## 
## --- BEND5 ; BF(dB)= 43.91835 ; M_beta= -0.2428747 
##     BEN Domain Containing 5 
## [1] "Acts as a transcriptional repressor (PubMed:23468431)."
## 
## --- MAP3K14 ; BF(dB)= 43.91835 ; M_beta= -0.2500272 
##     Mitogen-Activated Protein Kinase Kinase Kinase 14 
## [1] "Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner."
## 
## --- GATA5 ; BF(dB)= 43.91835 ; M_beta= -0.1807077 
##     GATA Binding Protein 5 
## [1] "Transcription factor required during cardiovascular development (PubMed:23289003). Plays an important role in the transcriptional program(s) that underlies smooth muscle cell diversity (By similarity). Binds to the functionally important CEF-1 nuclear protein binding site in the cardiac-specific slow/cardiac troponin C transcriptional enhancer (PubMed:25543888)."
## 
## --- RBM42 ; BF(dB)= 43.91835 ; M_beta= -0.2378254 
##     RNA Binding Motif Protein 42 
## [1] "Binds (via the RRM domain) to the 3'-untranslated region (UTR) of CDKN1A mRNA."
## 
## --- ZBTB3 ; BF(dB)= 42.94488 ; M_beta= -0.2417529 
##     Zinc Finger And BTB Domain Containing 3 
## [1] "May be involved in transcriptional regulation."
## 
## --- BRCA2 ; BF(dB)= 42.94488 ; M_beta= -0.2421726 
##     BRCA2 DNA Repair Associated 
## [1] "BRCA2 homolog to C elegans T07E3 uncharacterized gene,expressed in many tissues and most abundant in the S phase,complexing and interacting with phosphorylated BRCA1,RAD51 and RAD52 for cell cycle control and DNA repair through homologous recombination,also involved in embryonic cellular proliferation"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
## [2] "Involved in double-strand break repair and/or homologous recombination. Binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded HR complex containing RAD51C and which is thought to play a role in DNA repair by HR. May participate in S phase checkpoint activation. Binds selectively to ssDNA, and to ssDNA in tailed duplexes and replication fork structures. May play a role in the extension step after strand invasion at replication-dependent DNA double-strand breaks; together with PALB2 is involved in both POLH localization at collapsed replication forks and DNA polymerization activity. In concert with NPM1, regulates centrosome duplication. Interacts with the TREX-2 complex (transcription and export complex 2) subunits PCID2 and SEM1, and is required to prevent R-loop-associated DNA damage and thus transcription-associated genomic instability. Silencing of BRCA2 promotes R-loop accumulation at actively transcribed genes in replicating and non-replicating cells, suggesting that BRCA2 mediates the control of R-loop associated genomic instability, independently of its known role in homologous recombination (PubMed:24896180)."
## 
## --- MAPK8IP3 ; BF(dB)= 42.94488 ; M_beta= 0.2296149 
##     Mitogen-Activated Protein Kinase 8 Interacting Protein 3 
## [1] "The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:12189133). May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Promotes neuronal axon elongation in a kinesin- and JNK-dependent manner. Activates cofilin at axon tips via local activation of JNK, thereby regulating filopodial dynamics and enhancing axon elongation. Its binding to kinesin heavy chains (KHC), promotes kinesin-1 motility along microtubules and is essential for axon elongation and regeneration. Regulates cortical neuronal migration by mediating NTRK2/TRKB anterograde axonal transport during brain development (By similarity). Acts as an adapter that bridges the interaction between NTRK2/TRKB and KLC1 and drives NTRK2/TRKB axonal but not dendritic anterograde transport, which is essential for subsequent BDNF-triggered signaling and filopodia formation (PubMed:21775604)."
## 
## --- COLQ ; BF(dB)= 42.94488 ; M_beta= 0.2078199 
##     Collagen Like Tail Subunit Of Asymmetric Acetylcholinesterase 
## [1] "Anchors the catalytic subunits of asymmetric AChE to the synaptic basal lamina."                                                    
## [2] "collagen-like tail subunity,single strand of an homotrimer of the asymetric acetylcholinesterase,anchoring it into the basal lamina"
## 
## --- SI ; BF(dB)= 42.94488 ; M_beta= -0.2104189 
##     Sucrase-Isomaltase 
## [1] "sucrase-isomaltase,alpha D-glucosidase from intestinal mucosa that hydrolyzes sucrose and isomaltose,member of the glycosyl hydrolase family 3"           
## [2] "Plays an important role in the final stage of carbohydrate digestion. Isomaltase activity is specific for both alpha-1,4- and alpha-1,6-oligosaccharides."
## 
## --- NUP98 ; BF(dB)= 42.94488 ; M_beta= -0.2025426 
##     Nucleoporin 98 And 96 Precursor 
## [1] "Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. NUP98 and NUP96 are involved in the bidirectional transport across the NPC. May anchor NUP153 and TPR to the NPC. In cooperation with DHX9, plays a role in transcription and alternative splicing activation of a subset of genes (PubMed:28221134). Involved in the localization of DHX9 in discrete intranuclear foci (GLFG-body) (PubMed:28221134)."                                                                                                            
## [2] "(Microbial infection) Binds HIV-1 capsid-nucleocapsid (HIV-1 CA-NC) complexes and may thereby promote the integration of the virus in the host nucleus (in vitro) (PubMed:23523133). Binding affinity to HIV-1 CA-NC complexes bearing the capsid change ASN-74-ASP is reduced (in vitro) (PubMed:23523133)."                                                                                                                                                                                                                                   
## [3] "nucleoporin,essential component of multiple RNA export pathway,unlikely involved in the nuclear import of protein,fused with HOX9D in acute myeloid leukemia with translocation t(7;11) (p15;p15),and with DDX10 in de novo or therapy related myeloid malignancies with HOXD13 in translocation t(2;11) (q35;p15) with inv11(p15-q22) and with PMX1 in translocation t(1;11) (q23;p15),with RAP1GDS1 in t(4;11)(q21;p15) in T cell acute lymphocitic leukemia,fused with TOP1 in t(11;20)(p15;q11) in therapy related myelodysplastic syndrome"
## 
## --- FAT3 ; BF(dB)= 42.94488 ; M_beta= 0.1444237 
##     FAT Atypical Cadherin 3 
## [1] "May play a role in the interactions between neurites derived from specific subsets of neurons during development."
## 
## --- ZNF556 ; BF(dB)= 42.94488 ; M_beta= -0.1371081 
##     Zinc Finger Protein 556 
## [1] "May be involved in transcriptional regulation."
## 
## --- DUS3L ; BF(dB)= 42.94488 ; M_beta= -0.2540696 
##     Dihydrouridine Synthase 3 Like 
## [1] "Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs."
## 
## --- PRR22 ; BF(dB)= 42.94488 ; M_beta= -0.2540696 
##      
## character(0)
## 
## --- UBE2V1 ; BF(dB)= 42.94488 39.9127 ; M_beta= -0.1993587 -0.1999457 
##     Ubiquitin Conjugating Enzyme E2 V1 
## [1] "Has no ubiquitin ligase activity on its own. The UBE2V1-UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through Lys-63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes. Together with RNF135 and UBE2N, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIG-I/DDX58 to activate the downstream signaling pathway that leads to interferon beta production (PubMed:31006531). UBE2V1-UBE2N together with TRAF3IP2 E3 ubiquitin ligase mediate 'Lys-63'-linked polyubiquitination of TRAF6, a component of IL17A-mediated signaling pathway."
## [2] "Down-regulated during differentiation of cultured colon adenocarcinoma cells."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
## [3] "ubiquitin conjugating enzyme E2 variant 1,expressed as at least four isoforms,transcriptional activator of FOS promoter,underexpressed in hormone refractory prostate cancer,potentially involved in the control of differentiation"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
## 
## --- TMEM189 ; BF(dB)= 42.94488 39.9127 ; M_beta= -0.1993587 -0.1999457 
##      
## character(0)
## 
## --- ZBTB40 ; BF(dB)= 42.1487 ; M_beta= 0.2393652 
##     Zinc Finger And BTB Domain Containing 40 
## [1] "May be involved in transcriptional regulation."
## 
## --- FBXL20 ; BF(dB)= 42.1487 ; M_beta= 0.2063842 
##     F-Box And Leucine Rich Repeat Protein 20 
## [1] "Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Role in neural transmission (By similarity)."
## 
## --- ALK ; BF(dB)= 42.1487 ; M_beta= 0.2067917 
##     ALK Receptor Tyrosine Kinase 
## [1] "anaplastic (CD30 + large cell) lymphoma kinase playing an important role in brain development,involved in anaplastic nodal non Hodgkin lymphoma or Hodgkin disease with translocation t(2;5)(p23;q35) or inv2(23;q35),see NPM1"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
## [2] "Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK. Thinness gene involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity)."
## [3] "Activated by ligand-binding and subsequent phosphorylation. Inactivated through dephosphorylation by receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) when there is no stimulation by a ligand. Staurosporine, crizotinib and CH5424802 act as inhibitors of ALK kinase activity."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
## 
## --- DOCK10 ; BF(dB)= 42.1487 ; M_beta= -0.1971883 
##     Dedicator Of Cytokinesis 10 
## [1] "Guanine nucleotide-exchange factor (GEF) that activates CDC42 and RAC1 by exchanging bound GDP for free GTP. Essential for dendritic spine morphogenesis in Purkinje cells and in hippocampal neurons, via a CDC42-mediated pathway. Sustains B-cell lymphopoiesis in secondary lymphoid tissues and regulates FCER2/CD23 expression."
## [2] "Isoforms 1 and 2 are up-regulated in response to IL4 in B-cells but not T-cells."                                                                                                                                                                                                                                                     
## 
## --- MAPK12 ; BF(dB)= 42.1487 ; M_beta= -0.1780339 
##     Mitogen-Activated Protein Kinase 12 
## [1] "mitogen-activated protein kinase 12"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
## [2] "Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK12 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in myoblast differentiation and also in the down-regulation of cyclin D1 in response to hypoxia in adrenal cells suggesting MAPK12 may inhibit cell proliferation while promoting differentiation. Phosphorylates DLG1. Following osmotic shock, MAPK12 in the cell nucleus increases its association with nuclear DLG1, thereby causing dissociation of DLG1-SFPQ complexes. This function is independent of its catalytic activity and could affect mRNA processing and/or gene transcription to aid cell adaptation to osmolarity changes in the environment. Regulates UV-induced checkpoint signaling and repair of UV-induced DNA damage and G2 arrest after gamma-radiation exposure. MAPK12 is involved in the regulation of SLC2A1 expression and basal glucose uptake in L6 myotubes; and negatively regulates SLC2A4 expression and contraction-mediated glucose uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is stimulated by MAPK14 and inhibited by MAPK12, leading to a distinct AP-1 regulation. MAPK12 is required for the normal kinetochore localization of PLK1, prevents chromosomal instability and supports mitotic cell viability. MAPK12-signaling is also positively regulating the expansion of transient amplifying myogenic precursor cells during muscle growth and regeneration."
## [3] "Expression of MAPK12 is down-regulation by MAPK14 activation."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
## [4] "Activated by phosphorylation on threonine and tyrosine. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK12 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK12 activator in response to TNF-alpha."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
## 
## --- EFCAB2 ; BF(dB)= 41.47486 ; M_beta= 0.2298721 
##     EF-Hand Calcium Binding Domain 2 
## [1] "Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes."
## 
## --- MPC1 ; BF(dB)= 41.47486 ; M_beta= 0.2057792 
##     Mitochondrial Pyruvate Carrier 1 
## [1] "Mediates the uptake of pyruvate into mitochondria."
## 
## --- ATP9B ; BF(dB)= 41.47486 ; M_beta= -0.2382876 
##     ATPase Phospholipid Transporting 9B (Putative) 
## character(0)
## 
## --- UGGT1 ; BF(dB)= 41.47486 ; M_beta= 0.1894407 
##     UDP-Glucose Glycoprotein Glucosyltransferase 1 
## [1] "Recognizes glycoproteins with minor folding defects. Reglucosylates single N-glycans near the misfolded part of the protein, thus providing quality control for protein folding in the endoplasmic reticulum. Reglucosylated proteins are recognized by calreticulin for recycling to the endoplasmic reticulum and refolding or degradation."
## [2] "By tunicamycin and A23187. Induced 3-4 fold 10 hours after treatment."                                                                                                                                                                                                                                                                        
## [3] "Catalytic activity is enhanced by complex formation with SELENOF."                                                                                                                                                                                                                                                                            
## 
## --- ZNF213 ; BF(dB)= 41.47486 ; M_beta= 0.2376542 
##     Zinc Finger Protein 213 
## [1] "May be involved in transcriptional regulation."                         
## [2] "zinc finger protein 213 (C2H2 type,Kruppel-like),ubiquitously expressed"
## 
## --- ZNF233 ; BF(dB)= 41.47486 ; M_beta= 0.2086256 
##     Zinc Finger Protein 233 
## [1] "May be involved in transcriptional regulation."
## 
## --- ZNF235 ; BF(dB)= 41.47486 ; M_beta= 0.2086256 
##     Zinc Finger Protein 235 
## [1] "May be involved in transcriptional regulation."
## 
## --- PPP1R11 ; BF(dB)= 41.47486 ; M_beta= -0.2037899 
##     Protein Phosphatase 1 Regulatory Inhibitor Subunit 11 
## [1] "Atypical E3 ubiquitin-protein ligase which ubiquitinates TLR2 at 'Lys-754' leading to its degradation by the proteasome. Plays a role in regulating inflammatory cytokine release and gram-positive bacterial clearance by functioning, in part, through the ubiquitination and degradation of TLR2 (PubMed:27805901). Inhibitor of protein phosphatase 1 (PubMed:9843442)."
## [2] "protein phosphatase 1,regulatory (inhibitor) subunit 11,t-complex associated, expressed in testis,mouse Tctex 5 homolog,with a calculator mass of 14kDa and an apparent mass of 23kDa"                                                                                                                                                                                      
## 
## --- ZNRD1 ; BF(dB)= 41.47486 ; M_beta= -0.2037899 
##      
## character(0)
## 
## --- TTC3 ; BF(dB)= 40.89057 ; M_beta= -0.2218514 
##     Tetratricopeptide Repeat Domain 3 
## [1] "tetratricopeptide-repeat containing gene isoform 3,on the Down syndrome critical region,predominantly expressed in the central nervous system"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
## [2] "E3 ubiquitin-protein ligase which catalyzes the formation of 'Lys-48'-polyubiquitin chains (PubMed:20059950, PubMed:30696809). Mediates the ubiquitination and subsequent degradation of phosphorylated Akt (AKT1, AKT2 and AKT3) in the nucleus (PubMed:20059950). Acts as a terminal regulator of Akt signaling after activation; its phosphorylation by Akt, which is a prerequisite for ubiquitin ligase activity, suggests the existence of a regulation mechanism required to control Akt levels after activation (PubMed:20059950). Positively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation by mediating the ubiquitination and subsequent degradation of SMURF2 (PubMed:30696809). Regulates neuronal differentiation by regulating actin remodeling and Golgi organization via a signaling cascade involving RHOA, CIT and ROCK (PubMed:17488780, PubMed:24695496). Inhibits cell proliferation (PubMed:30203323)."
## [3] "Up-regulated by TGFB1 signaling."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
## 
## --- MAMDC2 ; BF(dB)= 40.89057 ; M_beta= -0.217845 
##      
## character(0)
## 
## --- AJUBA ; BF(dB)= 40.89057 ; M_beta= -0.247599 
##     Ajuba LIM Protein 
## [1] "Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, mitosis, cell-cell adhesion, cell differentiation, proliferation and migration. Contributes to the linking and/or strengthening of epithelia cell-cell junctions in part by linking adhesive receptors to the actin cytoskeleton. May be involved in signal transduction from cell adhesion sites to the nucleus. Plays an important role in regulation of the kinase activity of AURKA for mitotic commitment. Also a component of the IL-1 signaling pathway modulating IL-1-induced NFKB1 activation by influencing the assembly and activity of the PRKCZ-SQSTM1-TRAF6 multiprotein signaling complex. Functions as an HDAC-dependent corepressor for a subset of GFI1 target genes. Acts as a transcriptional corepressor for SNAI1 and SNAI2/SLUG-dependent repression of E-cadherin transcription. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Positively regulates microRNA (miRNA)-mediated gene silencing. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1."
## 
## --- CNTROB ; BF(dB)= 40.89057 ; M_beta= 0.1957425 
##     Centrobin, Centriole Duplication And Spindle Assembly Protein 
## [1] "Required for centriole duplication. Inhibition of centriole duplication leading to defects in cytokinesis."
## 
## --- MFSD12 ; BF(dB)= 40.89057 ; M_beta= -0.1886372 
##     Major Facilitator Superfamily Domain Containing 12 
## [1] "Transporter that mediates the import of cysteine into melanosomes, thereby regulating skin pigmentation (PubMed:33208952). In melanosomes, cysteine import is required both for normal levels of cystine, the oxidized dimer of cysteine, and provide cysteine for the production of the cysteinyldopas used in pheomelanin synthesis, thereby regulating skin pigmentation (PubMed:33208952). Also catalyzes import of cysteine into lysosomes in non-pigmented cells (PubMed:33208952)."
## 
## --- HMG20B ; BF(dB)= 40.89057 ; M_beta= -0.1886372 
##     High Mobility Group 20B 
## [1] "Required for correct progression through G2 phase of the cell cycle and entry into mitosis. Required for RCOR1/CoREST mediated repression of neuronal specific gene promoters."
## 
## --- SPTBN5 ; BF(dB)= 40.89057 ; M_beta= 0.1848624 
##      
## character(0)
## 
## --- SECISBP2L ; BF(dB)= 40.37466 ; M_beta= 0.1390687 
##     SECIS Binding Protein 2 Like 
## [1] "Binds SECIS (Sec insertion sequence) elements present on selenocysteine (Sec) protein mRNAs, but does not promote Sec incorporation into selenoproteins in vitro."
## 
## --- PANK4 ; BF(dB)= 40.37466 ; M_beta= 0.2500678 
##     Pantothenate Kinase 4 (Inactive) 
## [1] "May play a role in the physiological regulation of coenzyme A (CoA) intracellular levels (Probable). The phosphatase activity shows preference for normal or oxidatively damaged intermediates of 4'-phosphopantetheine, which provides strong indirect evidence that the phosphatase activity pre-empts damage in the CoA pathway (PubMed:27322068). Hydrolyzing excess 4'-phosphopantetheine could constitute a directed overflow mechanism to prevent its oxidation to the S-sulfonate, sulfonate, or other forms (PubMed:27322068). Hydrolyzing 4'-phosphopantetheine sulfonate or S-sulfonate would forestall their conversion to inactive forms of CoA and acyl carrier protein (PubMed:27322068)."
## [2] "Activity is strongly promoted by Co(2+), Ni(2+), Mg(2+) and Mn(2+) (PubMed:27322068). Activity is inhibited by EDTA (PubMed:27322068)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
## 
## --- HDAC4 ; BF(dB)= 40.37466 ; M_beta= -0.23296 
##     Histone Deacetylase 4 
## [1] "Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Deacetylates HSPA1A and HSPA1B at 'Lys-77' leading to their preferential binding to co-chaperone STUB1 (PubMed:27708256)."
## 
## --- FAM71C ; BF(dB)= 39.9127 ; M_beta= -0.209915 
##      
## character(0)
## 
## --- ANKS1B ; BF(dB)= 39.9127 ; M_beta= -0.209915 
##     Ankyrin Repeat And Sterile Alpha Motif Domain Containing 1B 
## [1] "Isoform 2 may participate in the regulation of nucleoplasmic coilin protein interactions in neuronal and transformed cells."                                         
## [2] "Isoform 3 can regulate global protein synthesis by altering nucleolar numbers."                                                                                      
## [3] "Isoform 4 may play a role as a modulator of APP processing. Overexpression can down-regulate APP processing."                                                        
## [4] "Transcriptionally up-regulated in t(1:19) pre-B cell acute lymphocytic leukemia by the chimeric TCF3-PBX1. Not expressed in pre-B cell that lack this translocation."
## 
## --- C17ORF75 ; BF(dB)=  ; M_beta=  
##     Chromosome 17 Open Reading Frame 75 
## [1] "As component of the WDR11 complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles generated using AP-1 (PubMed:29426865). May have a role in spermatogenesis."
## 
## --- FXYD1 ; BF(dB)= 39.9127 ; M_beta= -0.2285893 
##     FXYD Domain Containing Ion Transport Regulator 1 
## [1] "Associates with and regulates the activity of the sodium/potassium-transporting ATPase (NKA) which transports Na(+) out of the cell and K(+) into the cell. Inhibits NKA activity in its unphosphorylated state and stimulates activity when phosphorylated. Reduces glutathionylation of the NKA beta-1 subunit ATP1B1, thus reversing glutathionylation-mediated inhibition of ATP1B1. Contributes to female sexual development by maintaining the excitability of neurons which secrete gonadotropin-releasing hormone."
## 
## --- LGI4 ; BF(dB)= 39.9127 ; M_beta= -0.2285893 
##     Leucine Rich Repeat LGI Family Member 4 
## [1] "Component of Schwann cell signaling pathway(s) that controls axon segregation and myelin formation (By similarity)."
## 
## --- DDR2 ; BF(dB)= 39.9127 ; M_beta= -0.1967691 
##     Discoidin Domain Receptor Tyrosine Kinase 2 
## [1] "discoidin domain recptor family,member 2,expressed in heart and lung"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
## [2] "Tyrosine kinase involved in the regulation of tissues remodeling (PubMed:30449416). It functions as cell surface receptor for fibrillar collagen and regulates cell differentiation, remodeling of the extracellular matrix, cell migration and cell proliferation. Required for normal bone development. Regulates osteoblast differentiation and chondrocyte maturation via a signaling pathway that involves MAP kinases and leads to the activation of the transcription factor RUNX2. Regulates remodeling of the extracellular matrix by up-regulation of the collagenases MMP1, MMP2 and MMP13, and thereby facilitates cell migration and tumor cell invasion. Promotes fibroblast migration and proliferation, and thereby contributes to cutaneous wound healing."
## [3] "Up-regulated during osteoblast differentiation (in vitro). Up-regulated in cartilage from osteoarthritis patients."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
## [4] "Present in an inactive state in the absence of collagen binding and phosphorylation by SRC. Tyrosine phosphorylation enhances the affinity for ATP and the catalytic activity."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
## 
## --- PHGDH ; BF(dB)= 39.49439 ; M_beta= -0.2128944 
##     Phosphoglycerate Dehydrogenase 
## [1] "Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L-serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of (S)-malate to oxaloacetate."
## [2] "Induced by 17-beta-estradiol (estrogenic ligand) and 4-hydroxytamoxifen (agonist/antagonist ligand). Positively regulated by the transcription factors SP1 and NF-Y."                                                                                                                                  
## 
## --- NEDD4L ; BF(dB)= 39.49439 ; M_beta= 0.2036655 
##     NEDD4 Like E3 Ubiquitin Protein Ligase 
## [1] "E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Inhibits TGF-beta signaling by triggering SMAD2 and TGFBR1 ubiquitination and proteasome-dependent degradation. Promotes ubiquitination and internalization of various plasma membrane channels such as ENaC, SCN2A/Nav1.2, SCN3A/Nav1.3, SCN5A/Nav1.5, SCN9A/Nav1.7, SCN10A/Nav1.8, KCNA3/Kv1.3, KCNH2, EAAT1, KCNQ2/Kv7.2, KCNQ3/Kv7.3 or CLC5 (PubMed:26363003, PubMed:27445338). Promotes ubiquitination and degradation of SGK1 and TNK2. Ubiquitinates BRAT1 and this ubiquitination is enhanced in the presence of NDFIP1 (PubMed:25631046). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Involved in the regulation of TOR signaling (PubMed:27694961). Ubiquitinates and regulates protein levels of NTRK1 once this one is activated by NGF (PubMed:27445338)."
## [2] "By androgens in prostate, and by albumin in kidney."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
## [3] "Activated by NDFIP1- and NDFIP2-binding."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
## [4] "neural precursor cell expressed gene 4-like,developmentally down-regulated 4-like"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
## 
## --- TMEM119 ; BF(dB)= 39.49439 ; M_beta= -0.1783402 
##     Transmembrane Protein 119 
## [1] "Plays an important role in bone formation and normal bone mineralization. Promotes the differentiation of myoblasts into osteoblasts (PubMed:20025746). May induce the commitment and differentiation of myoblasts into osteoblasts through an enhancement of BMP2 production and interaction with the BMP-RUNX2 pathway. Upregulates the expression of ATF4, a transcription factor which plays a central role in osteoblast differentiation. Essential for normal spermatogenesis and late testicular differentiation (By similarity)."
## 
## --- NEB ; BF(dB)= 39.49439 ; M_beta= -0.1814495 
##     Nebulin 
## [1] "nebulin,helical actin binding protein,of the skeletal muscle,involved in the length regulation of the thin filament"                                                                 
## [2] "This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils. Binds and stabilize F-actin."
## 
## --- FZD4 ; BF(dB)= 39.49439 ; M_beta= -0.177147 
##     Frizzled Class Receptor 4 
## [1] "Drosophila frizzled polarity gene homolog 4,G protein coupled receptor superfamily,exhibiting characteristics of a WNT receptor,widely expressed and predominantly in fetal kidney,adult heart,skeletal muscle and ovary"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
## [2] "Receptor for Wnt proteins (PubMed:30135577). Most frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes (PubMed:30135577). Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP) (By similarity). In retina, it can be activated by Wnt protein-binding and also by Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs (By similarity). A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues."
## 
## --- PRSS23 ; BF(dB)= 39.49439 ; M_beta= -0.177147 
##     Serine Protease 23 
## character(0)
## 
## --- ZNF324B ; BF(dB)= 39.49439 ; M_beta= 0.2001209 
##     Zinc Finger Protein 324B 
## [1] "May be involved in transcriptional regulation."
## 
## --- BAZ1A ; BF(dB)= 39.11211 ; M_beta= -0.2258643 
##     Bromodomain Adjacent To Zinc Finger Domain 1A 
## [1] "Component of the ACF complex, an ATP-dependent chromatin remodeling complex, that regulates spacing of nucleosomes using ATP to generate evenly spaced nucleosomes along the chromatin. The ATPase activity of the complex is regulated by the length of flanking DNA. Also involved in facilitating the DNA replication process. BAZ1A is the accessory, non-catalytic subunit of the complex which can enhance and direct the process provided by the ATPase subunit, SMARCA5, probably through targeting pericentromeric heterochromatin in late S phase. Moves end-positioned nucleosomes to a predominantly central position. May have a role in nuclear receptor-mediated transcription repression."
## [2] "Component of the histone-fold protein complex CHRAC complex which facilitates nucleosome sliding by the ACF complex and enhances ACF-mediated chromatin assembly. The C-terminal regions of both CHRAC1 and POLE1 are required for these functions."                                                                                                                                                                                                                                                                                                                                                                                                                                                      
## 
## --- NIPAL1 ; BF(dB)= 39.11211 39.11211 ; M_beta= -0.1841561 -0.1911782 
##     NIPA Like Domain Containing 1 
## [1] "Acts as a Mg(2+) transporter. Can also transport other divalent cations such as Fe(2+), Sr(2+), Ba(2+), Mn(2+), Cu(2+) and Co(2+) but to a much less extent than Mg(2+) (By similarity)."
## 
## --- CNGA1 ; BF(dB)= 39.11211 39.11211 ; M_beta= -0.1841561 -0.1911782 
##     Cyclic Nucleotide Gated Channel Subunit Alpha 1 
## [1] "cyclic guanine nucleotide gated channel (cGMP),rod photoreceptor,expressed in the rod outer segment alpha 1 subunit,heterodimerizing with CNGB4"                                                                                                                                                       
## [2] "Subunit of the rod cyclic GMP-gated cation channel, which is involved in the final stage of the phototransduction pathway. When light hits rod photoreceptors, cGMP concentrations decrease causing rapid closure of CNGA1/CNGB1 channels and, therefore, hyperpolarization of the membrane potential."
## 
## --- NMBR ; BF(dB)= 39.11211 ; M_beta= 0.2157316 
##     Neuromedin B Receptor 
## [1] "Receptor for neuromedin-B."                                   
## [2] "neuromedin B receptor, G protein coupled receptor superfamily"
## 
## --- FREM1 ; BF(dB)= 39.11211 ; M_beta= -0.2290478 
##     FRAS1 Related Extracellular Matrix 1 
## [1] "Extracellular matrix protein that plays a role in epidermal differentiation and is required for epidermal adhesion during embryonic development."
## 
## --- TTLL7 ; BF(dB)= 39.11211 ; M_beta= 0.232441 
##     Tubulin Tyrosine Ligase Like 7 
## [1] "Polyglutamylase which preferentially modifies beta-tubulin (PubMed:25959773). Mediates both ATP-dependent initiation and elongation of polyglutamylation of microtubules (PubMed:25959773). Required for neurite growth; responsible for the strong increase in tubulin polyglutamylation during postnatal neuronal maturation (By similarity)."
## 
## --- TUBA3C ; BF(dB)= 39.11211 ; M_beta= -0.2215948 
##     Tubulin Alpha 3c 
## [1] "Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain."
## 
## --- ITGAE ; BF(dB)= 38.76009 ; M_beta= 0.1945923 
##     Integrin Subunit Alpha E 
## [1] "Integrin alpha-E/beta-7 is a receptor for E-cadherin. It mediates adhesion of intra-epithelial T-lymphocytes to epithelial cell monolayers."
## [2] "Integrin alpha-E/beta-7 is induced by TGFB1."                                                                                               
## 
## --- PHC3 ; BF(dB)= 38.76009 ; M_beta= -0.2112653 
##     Polyhomeotic Homolog 3 
## [1] "Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility."
## 
## --- GPR160 ; BF(dB)= 38.76009 ; M_beta= -0.2112653 
##     G Protein-Coupled Receptor 160 
## [1] "Orphan receptor."
## 
## --- MCF2L ; BF(dB)= 38.1298 ; M_beta= 0.2137808 
##     MCF.2 Cell Line Derived Transforming Sequence Like 
## [1] "Guanine nucleotide exchange factor that catalyzes guanine nucleotide exchange on RHOA and CDC42, and thereby contributes to the regulation of RHOA and CDC42 signaling pathways (By similarity). Seems to lack activity with RAC1. Becomes activated and highly tumorigenic by truncation of the N-terminus (By similarity). Isoform 5 activates CDC42 (PubMed:15157669)."
## [2] "[Isoform 3]: Does not catalyze guanine nucleotide exchange on CDC42 (PubMed:15157669)."                                                                                                                                                                                                                                                                                   
## 
## --- PRPF8 ; BF(dB)= 37.8451 ; M_beta= -0.2377216 
##     Pre-MRNA Processing Factor 8 
## [1] "Plays role in pre-mRNA splicing as core component of precatalytic, catalytic and postcatalytic spliceosomal complexes, both of the predominant U2-type spliceosome and the minor U12-type spliceosome (PubMed:10411133, PubMed:11971955, PubMed:28502770, PubMed:28781166, PubMed:28076346, PubMed:29361316, PubMed:30315277, PubMed:29360106, PubMed:29301961, PubMed:30728453, PubMed:30705154). Functions as a scaffold that mediates the ordered assembly of spliceosomal proteins and snRNAs. Required for the assembly of the U4/U6-U5 tri-snRNP complex, a building block of the spliceosome. Functions as scaffold that positions spliceosomal U2, U5 and U6 snRNAs at splice sites on pre-mRNA substrates, so that splicing can occur. Interacts with both the 5' and the 3' splice site."
## 
## --- ce  missing genes
## [1] "PRR22"   "TMEM189" "ZNRD1"   "MAMDC2"  "SPTBN5"  "FAM71C" 
## 
## 
## 
## 
## - w 
## -- f_over_sum_known_trees 
## --- BEST2 ; BF(dB)= 40.89057 ; M_beta= 0.1733309 
##     Bestrophin 2 
## [1] "Forms calcium-sensitive chloride channels. Permeable to bicarbonate."
## 
## --- CLSTN3 ; BF(dB)= 36.23802 ; M_beta= 0.1707913 
##     Calsyntenin 3 
## [1] "May modulate calcium-mediated postsynaptic signals. Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2-mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation."
## 
## --- ADAM18 ; BF(dB)= 35.36143 25.08229 ; M_beta= 0.2185704 0.1603033 
##     ADAM Metallopeptidase Domain 18 
## [1] "Sperm surface membrane protein that may be involved in spermatogenesis and fertilization. This is a non catalytic metalloprotease-like protein (By similarity)."
## 
## --- SEMA3A ; BF(dB)= 32.65331 ; M_beta= 0.1675469 
##     Semaphorin 3A 
## [1] "Involved in the development of the olfactory system and in neuronal control of puberty. Induces the collapse and paralysis of neuronal growth cones. Could serve as a ligand that guides specific growth cones by a motility-inhibiting mechanism. Binds to the complex neuropilin-1/plexin-1."
## [2] "semaphorin 3A,secreted,repellent of the nerve growth cone guidance"                                                                                                                                                                                                                            
## 
## --- ZNF48 ; BF(dB)= 31.98373 ; M_beta= -0.2146088 
##     Zinc Finger Protein 48 
## [1] "zinc finger protein 48 (C2H2 type,Kruppel-like)"
## [2] "May be involved in transcriptional regulation." 
## 
## --- SEPT1 ; BF(dB)= 31.98373 ; M_beta= -0.2146088 
##      
## character(0)
## 
## --- USP6 ; BF(dB)= 31.82971 ; M_beta= 0.1986122 
##     Ubiquitin Specific Peptidase 6 
## [1] "Deubiquitinase with an ATP-independent isopeptidase activity, cleaving at the C-terminus of the ubiquitin moiety. Catalyzes its own deubiquitination. In vitro, isoform 2, but not isoform 3, shows deubiquitinating activity. Promotes plasma membrane localization of ARF6 and selectively regulates ARF6-dependent endocytic protein trafficking. Is able to initiate tumorigenesis by inducing the production of matrix metalloproteinases following NF-kappa-B activation."
## [2] "ubiquitin specific protease 6,hyperpolymorphic gene 1,deubiquitin enzyme family"                                                                                                                                                                                                                                                                                                                                                                                                
## 
## --- MYH9 ; BF(dB)= 30.74346 ; M_beta= 0.219925 
##     Myosin Heavy Chain 9 
## [1] "myosin,motor contractile protein moving towards the \"\"plus\"\" end of actin track,heavy polypeptide 9,non muscle"                                                                                                                                                                                                                                                                                                                                                                                                                                              
## [2] "Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping. Required for cortical actin clearance prior to oocyte exocytosis (By similarity). Promotes cell motility in conjunction with S100A4 (PubMed:16707441). During cell spreading, plays an important role in cytoskeleton reorganization, focal contact formation (in the margins but not the central part of spreading cells), and lamellipodial retraction; this function is mechanically antagonized by MYH10 (PubMed:20052411)."
## 
## --- RFFL ; BF(dB)= 30.27637 ; M_beta= -0.1979228 
##     Ring Finger And FYVE Like Domain Containing E3 Ubiquitin Protein Ligase 
## [1] "E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. Negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling."
## [2] "Down-regulated upon DNA damage."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
## 
## --- PANX1 ; BF(dB)= 29.95158 ; M_beta= 0.177335 
##     Pannexin 1 
## [1] "Structural component of the gap junctions and the hemichannels involved in the ATP release and nucleotide permeation (PubMed:16908669, PubMed:20829356, PubMed:30918116). May play a role as a Ca(2+)-leak channel to regulate ER Ca(2+) homeostasis (PubMed:16908669). Plays a critical role in oogenesis (PubMed:30918116)."
## 
## --- TMEM87B ; BF(dB)= 29.89933 ; M_beta= -0.1943812 
##     Transmembrane Protein 87B 
## [1] "May be involved in retrograde transport from endosomes to the trans-Golgi network (TGN)."
## 
## --- SMG1 ; BF(dB)= 29.79636 ; M_beta= 0.1902105 
##     SMG1 Nonsense Mediated MRNA Decay Associated PI3K Related Kinase 
## [1] "Serine/threonine protein kinase involved in both mRNA surveillance and genotoxic stress response pathways. Recognizes the substrate consensus sequence [ST]-Q. Plays a central role in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by phosphorylating UPF1/RENT1. Recruited by release factors to stalled ribosomes together with SMG8 and SMG9 (forming the SMG1C protein kinase complex), and UPF1 to form the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. In EJC-dependent NMD, the SURF complex associates with the exon junction complex (EJC) through UPF2 and allows the formation of an UPF1-UPF2-UPF3 surveillance complex which is believed to activate NMD. Also acts as a genotoxic stress-activated protein kinase that displays some functional overlap with ATM. Can phosphorylate p53/TP53 and is required for optimal p53/TP53 activation after cellular exposure to genotoxic stress. Its depletion leads to spontaneous DNA damage and increased sensitivity to ionizing radiation (IR). May activate PRKCI but not PRKCZ."
## [2] "Inhibited by caffeine, LY294002 and wortmannin."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
## 
## --- TNPO2 ; BF(dB)= 29.7456 ; M_beta= 0.1235457 
##     Transportin 2 
## [1] "Probably functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity)."
## 
## --- TTC3 ; BF(dB)= 29.54725 27.25563 ; M_beta= 0.1487807 0.1395552 
##     Tetratricopeptide Repeat Domain 3 
## [1] "tetratricopeptide-repeat containing gene isoform 3,on the Down syndrome critical region,predominantly expressed in the central nervous system"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
## [2] "E3 ubiquitin-protein ligase which catalyzes the formation of 'Lys-48'-polyubiquitin chains (PubMed:20059950, PubMed:30696809). Mediates the ubiquitination and subsequent degradation of phosphorylated Akt (AKT1, AKT2 and AKT3) in the nucleus (PubMed:20059950). Acts as a terminal regulator of Akt signaling after activation; its phosphorylation by Akt, which is a prerequisite for ubiquitin ligase activity, suggests the existence of a regulation mechanism required to control Akt levels after activation (PubMed:20059950). Positively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation by mediating the ubiquitination and subsequent degradation of SMURF2 (PubMed:30696809). Regulates neuronal differentiation by regulating actin remodeling and Golgi organization via a signaling cascade involving RHOA, CIT and ROCK (PubMed:17488780, PubMed:24695496). Inhibits cell proliferation (PubMed:30203323)."
## [3] "Up-regulated by TGFB1 signaling."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
## 
## --- SYNE2 ; BF(dB)= 29.3559 ; M_beta= -0.2004538 
##     Spectrin Repeat Containing Nuclear Envelope Protein 2 
## [1] "Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization. As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. May be involved in nucleus-centrosome attachment. During interkinetic nuclear migration (INM) at G2 phase and nuclear migration in neural progenitors its LINC complex association with SUN1/2 and probable association with cytoplasmic dynein-dynactin motor complexes functions to pull the nucleus toward the centrosome; SYNE1 and SYNE2 may act redundantly. During INM at G1 phase mediates respective LINC complex association with kinesin to push the nucleus away from the centrosome. Involved in nuclear migration in retinal photoreceptor progenitors. Required for centrosome migration to the apical cell surface during early ciliogenesis."
## 
## --- ESR2 ; BF(dB)= 29.3559 ; M_beta= -0.2004538 
##     Estrogen Receptor 2 
## [1] "estrogen receptor beta,steroid/thyroid receptor superfamily,with several alternatively spliced isoforms (hER beta 1-5),expressed in thymus,spleen,ovary and testis, not rearranged in uterine leiomyomata,see ULCR14"                  
## [2] "Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560)."
## [3] "[Isoform 2]: Lacks ligand binding ability and has no or only very low ERE binding activity resulting in the loss of ligand-dependent transactivation ability."                                                                         
## 
## --- MYO15A ; BF(dB)= 29.03633 23.76093 ; M_beta= -0.1809397 0.08169343 
##     Myosin XVA 
## [1] "Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Required for the arrangement of stereocilia in mature hair bundles (By similarity)."
## 
## --- ASNA1 ; BF(dB)= 28.99214 ; M_beta= 0.1933267 
##      
## character(0)
## 
## --- C19ORF43 ; BF(dB)=  ; M_beta=  
##      
## character(0)
## 
## --- MAN2B1 ; BF(dB)= 28.99214 ; M_beta= 0.1574988 
##     Mannosidase Alpha Class 2B Member 1 
## [1] "mannosidase alpha B isoform,exoglycosidase,110kDa,lysosomal,Golgi,involved in processing of Asp-linked (N) glycans"                                 
## [2] "Necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover. Cleaves all known types of alpha-mannosidic linkages."
## 
## --- DDX11 ; BF(dB)= 28.32846 ; M_beta= 0.1708502 
##     DEAD/H-Box Helicase 11 
## [1] "DNA-dependent ATPase and ATP-dependent DNA helicase that participates in various functions in genomic stability, including DNA replication, DNA repair and heterochromatin organization as well as in ribosomal RNA synthesis (PubMed:10648783, PubMed:21854770, PubMed:23797032, PubMed:26089203, PubMed:26503245). Its double-stranded DNA helicase activity requires either a minimal 5'-single-stranded tail length of approximately 15 nt (flap substrates) or 10 nt length single-stranded gapped DNA substrates of a partial duplex DNA structure for helicase loading and translocation along DNA in a 5' to 3' direction (PubMed:18499658, PubMed:22102414). The helicase activity is capable of displacing duplex regions up to 100 bp, which can be extended up to 500 bp by the replication protein A (RPA) or the cohesion CTF18-replication factor C (Ctf18-RFC) complex activities (PubMed:18499658). Shows also ATPase- and helicase activities on substrates that mimic key DNA intermediates of replication, repair and homologous recombination reactions, including forked duplex, anti-parallel G-quadruplex and three-stranded D-loop DNA molecules (PubMed:22102414, PubMed:26503245). Plays a role in DNA double-strand break (DSB) repair at the DNA replication fork during DNA replication recovery from DNA damage (PubMed:23797032). Recruited with TIMELESS factor upon DNA-replication stress response at DNA replication fork to preserve replication fork progression, and hence ensure DNA replication fidelity (PubMed:26503245). Cooperates also with TIMELESS factor during DNA replication to regulate proper sister chromatid cohesion and mitotic chromosome segregation (PubMed:17105772, PubMed:18499658, PubMed:20124417, PubMed:23116066, PubMed:23797032). Stimulates 5'-single-stranded DNA flap endonuclease activity of FEN1 in an ATP- and helicase-independent manner; and hence it may contribute in Okazaki fragment processing at DNA replication fork during lagging strand DNA synthesis (PubMed:18499658). Its ability to function at DNA replication fork is modulated by its binding to long non-coding RNA (lncRNA) cohesion regulator non-coding RNA DDX11-AS1/CONCR, which is able to increase both DDX11 ATPase activity and binding to DNA replicating regions (PubMed:27477908). Plays also a role in heterochromatin organization (PubMed:21854770). Involved in rRNA transcription activation through binding to active hypomethylated rDNA gene loci by recruiting UBTF and the RNA polymerase Pol I transcriptional machinery (PubMed:26089203). Plays a role in embryonic development and prevention of aneuploidy (By similarity). Involved in melanoma cell proliferation and survival (PubMed:23116066). Associates with chromatin at DNA replication fork regions (PubMed:27477908). Binds to single- and double-stranded DNAs (PubMed:9013641, PubMed:18499658, PubMed:22102414)."
## [2] "(Microbial infection) Required for bovine papillomavirus type 1 regulatory protein E2 loading onto mitotic chromosomes during DNA replication for the viral genome to be maintained and segregated."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
## [3] "Up-regulated by serum (at protein level) (PubMed:26089203). Up-regulated by fibroblast growth factor FGF7 (PubMed:8798685). Expressed in keratinocyte growth factor-stimulated cells but not in EGF and IL1-beta-treated keratinocytes (PubMed:8798685). Up-regulated with progression from noninvasive to invasive melanoma (PubMed:23116066)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
## [4] "ATPase activity is stimulated by high magnesium salt levels (up to a 0.1 M), and potassium salts (glutamate, chloride or acetate) are more effective than the corresponding sodium salts (PubMed:10648783, PubMed:18499658). ATPase activity is enhanced by the long non-coding RNA (lncRNA) cohesion regulator noncoding RNA (CONCR) (PubMed:27477908). Double-stranded DNA helicase activity is maximal with magnesium ions at low concentrations (0.5-1 mM) whereas is markedly inhibited at higher levels (5 mM and above) (PubMed:10648783, PubMed:18499658). Double-stranded DNA helicase activity is stimulated by 25-50 mM potassium acetate, stimulated to a lesser extent by 25 mM of ammonium acetate, and markedly inhibited by sodium acetate (PubMed:18499658)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
## [5] "DEAD/H box protein 11,yeast Chl1 related-helicase gene 1,putative regulator of chromosome segregation and transmission"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
## 
## --- EPHB2 ; BF(dB)= 28.28942 ; M_beta= 0.1369236 
##     EPH Receptor B2 
## [1] "Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Functions in axon guidance during development. Involved in the guidance of commissural axons, that form a major interhemispheric connection between the 2 temporal lobes of the cerebral cortex. Also involved in guidance of contralateral inner ear efferent growth cones at the midline and of retinal ganglion cell axons to the optic disk. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses. Upon activation by EFNB1, abolishes the ARHGEF15-mediated negative regulation on excitatory synapse formation. Controls other aspects of development including angiogenesis, palate development and in inner ear development through regulation of endolymph production. Forward and reverse signaling through the EFNB2/EPHB2 complex regulate movement and adhesion of cells that tubularize the urethra and septate the cloaca. May function as a tumor suppressor. May be involved in the regulation of platelet activation and blood coagulation (PubMed:30213874)."
## [2] "EPH-related tyrosine kinase receptor,binding ephrins B,expressed in projecting neurons and their target fields,involved in short-range contact-mediated axonal guidance,developmentally regulated,expressed in brain,and other tissues,likely involved in neurogenesis and oncogenesis (neuroblastoma,SCLC),phosphorylating and interacting with RRAS to control integrin activity"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
## 
## --- GYPB ; BF(dB)= 28.06048 ; M_beta= 0.1872662 
##     Glycophorin B (MNS Blood Group) 
## [1] "glycophorin B (Ss specifity)"                                       
## [2] "This protein is a minor sialoglycoprotein in erythrocyte membranes."
## 
## --- GYPA ; BF(dB)= 28.06048 ; M_beta= 0.1872662 
##     Glycophorin A (MNS Blood Group) 
## [1] "glycophorin A (MN specificity),erythroid specific"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
## [2] "Glycophorin A is the major intrinsic membrane protein of the erythrocyte. The N-terminal glycosylated segment, which lies outside the erythrocyte membrane, has MN blood group receptors. Appears to be important for the function of SLC4A1 and is required for high activity of SLC4A1. May be involved in translocation of SLC4A1 to the plasma membrane. Is a receptor for influenza virus. Is a receptor for Plasmodium falciparum erythrocyte-binding antigen 175 (EBA-175); binding of EBA-175 is dependent on sialic acid residues of the O-linked glycans. Appears to be a receptor for Hepatitis A virus (HAV)."
## 
## --- FAHD2A ; BF(dB)= 27.94925 ; M_beta= -0.1992843 
##     Fumarylacetoacetate Hydrolase Domain Containing 2A 
## [1] "May have hydrolase activity."
## 
## --- SCN5A ; BF(dB)= 27.91263 ; M_beta= 0.2049969 
##     Sodium Voltage-Gated Channel Alpha Subunit 5 
## [1] "sodium voltage-gated channel,type V,alpha polypeptide,tetradotoxin-resistant,heart"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
## [2] "This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:1309946, PubMed:21447824, PubMed:25370050, PubMed:23420830, PubMed:23085483, PubMed:26279430, PubMed:26392562, PubMed:26776555). It is a tetrodotoxin-resistant Na(+) channel isoform (PubMed:1309946). This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels (PubMed:19074138)."
## 
## --- TAF4 ; BF(dB)= 27.87624 ; M_beta= -0.1992805 
##     TATA-Box Binding Protein Associated Factor 4 
## [1] "Part of the TFIID complex, a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. Potentiates transcriptional activation by the AF-2S of the retinoic acid, vitamin D3 and thyroid hormone."
## 
## --- MYO10 ; BF(dB)= 27.66233 ; M_beta= -0.2073268 
##     Myosin X 
## [1] "Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. MYO10 binds to actin filaments and actin bundles and functions as plus end-directed motor. The tail domain binds to membranous compartments containing phosphatidylinositol 3,4,5-trisphosphate or integrins, and mediates cargo transport along actin filaments. Regulates cell shape, cell spreading and cell adhesion. Stimulates the formation and elongation of filopodia. May play a role in neurite outgrowth and axon guidance. In hippocampal neurons it induces the formation of dendritic filopodia by trafficking the actin-remodeling protein VASP to the tips of filopodia, where it promotes actin elongation. Plays a role in formation of the podosome belt in osteoclasts."
## [2] "[Isoform Headless]: Functions as a dominant-negative regulator of isoform 1, suppressing its filopodia-inducing and axon outgrowth-promoting activities. In hippocampal neurons, it increases VASP retention in spine heads to induce spine formation and spine head expansion (By similarity)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
## [3] "myosin X,unconventional,apparently non filamentous,homologous to mouse Myo10,and porcine myosin VIIB"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
## 
## --- TMPRSS3 ; BF(dB)= 27.55813 ; M_beta= 0.1644484 
##     Transmembrane Serine Protease 3 
## [1] "Probable serine protease that plays a role in hearing. Acts as a permissive factor for cochlear hair cell survival and activation at the onset of hearing and is required for saccular hair cell survival (By similarity). Activates ENaC (in vitro)."
## 
## --- GPR39 ; BF(dB)= 27.55813 ; M_beta= 0.1730881 
##     G Protein-Coupled Receptor 39 
## [1] "G protein coupled receptor 39,with two forms generated by alternative polyadenylation sites,highly homolog to growth hormone,secretagogue receptor (GSHR) and neurotensin receptors,expressed in the brain and other tissues"                                                                                                                                    
## [2] "Zn(2+) acts as an agonist. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated mainly through G(q)-alpha and G(12)/G(13) proteins. Involved in regulation of body weight, gastrointestinal mobility, hormone secretion and cell death (By similarity)."
## 
## --- PPP1R21 ; BF(dB)= 27.48963 ; M_beta= -0.1694677 
##     Protein Phosphatase 1 Regulatory Subunit 21 
## [1] "Putative regulator of protein phosphatase 1 (PP1) activity (PubMed:19389623). May play a role in the endosomal sorting process or in endosome maturation pathway (PubMed:30520571)."
## 
## --- HSD17B7 ; BF(dB)= 27.2229 ; M_beta= 0.1741131 
##     Hydroxysteroid 17-Beta Dehydrogenase 7 
## [1] "Bifunctional enzyme involved in steroid-hormone metabolism and cholesterol biosynthesis (PubMed:12574203, PubMed:12732193, PubMed:12829805, PubMed:20659585, PubMed:19772289, PubMed:11165030). Catalyzes the NADP(H)-dependent reduction of estrogens and androgens and regulates the biological potency of these steroids. Converts estrone (E1) to a more potent estrogen, 17beta-estradiol (E2) (PubMed:12574203, PubMed:12732193, PubMed:19772289). Converts dihydrotestosterone (DHT) to its inactive form 5a-androstane-3b,17b-diol (PubMed:12574203, PubMed:12732193, PubMed:19772289). Converts moderately progesterone to 3beta-hydroxypregn-4-ene-20-one, leading to its inactivation (PubMed:12574203, PubMed:12732193). Additionally, participates in the post-squalene cholesterol biosynthesis, as a 3-ketosteroid reductase (PubMed:12829805, PubMed:20659585, PubMed:11165030)."
## [2] "[Isoform 3]: Does not have enzymatic activities toward E1 and DHT."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
## [3] "Estradiol 17-beta-dehydrogenase and dihydrotestosterone oxidoreductase activities are selectively inhibited by 4-methyl-4-aza-5alpha-androstane derivatives, such as 17beta-[(N-Heptyl)methylamino]-4-aza-5r-androstan-3-one and 17beta-(N-Decylformamido)-4-aza-5r-androstan-3-one."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
## [4] "17 beta hydroxysteroid dehydrogenase type 7,expressed in the corpus luteum during pregnancy,responsible for extradive biosynthesis"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
## 
## --- BAZ1A ; BF(dB)= 27.19034 ; M_beta= 0.1478759 
##     Bromodomain Adjacent To Zinc Finger Domain 1A 
## [1] "Component of the ACF complex, an ATP-dependent chromatin remodeling complex, that regulates spacing of nucleosomes using ATP to generate evenly spaced nucleosomes along the chromatin. The ATPase activity of the complex is regulated by the length of flanking DNA. Also involved in facilitating the DNA replication process. BAZ1A is the accessory, non-catalytic subunit of the complex which can enhance and direct the process provided by the ATPase subunit, SMARCA5, probably through targeting pericentromeric heterochromatin in late S phase. Moves end-positioned nucleosomes to a predominantly central position. May have a role in nuclear receptor-mediated transcription repression."
## [2] "Component of the histone-fold protein complex CHRAC complex which facilitates nucleosome sliding by the ACF complex and enhances ACF-mediated chromatin assembly. The C-terminal regions of both CHRAC1 and POLE1 are required for these functions."                                                                                                                                                                                                                                                                                                                                                                                                                                                      
## 
## --- SMPD2 ; BF(dB)= 27.02998 ; M_beta= 0.1633549 
##     Sphingomyelin Phosphodiesterase 2 
## [1] "Catalyzes the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Ceramide mediates numerous cellular functions, such as apoptosis and growth arrest, and is capable of regulating these 2 cellular events independently. Also hydrolyzes sphingosylphosphocholine. Hydrolyze 1-acyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PC) and 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-platelet-activating factor)."
## [2] "pH dependence: Optimum pH is 6.5-7.5.;"                                                                                                                                                                                                                                                                                                                                                                                            
## 
## --- MICAL1 ; BF(dB)= 27.02998 ; M_beta= 0.1633549 
##     Microtubule Associated Monooxygenase, Calponin And LIM Domain Containing 1 
## [1] "Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization (By similarity). In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2) (PubMed:21864500, PubMed:26845023). Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments. Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4. Involved in regulation of lamina-specific connectivity in the nervous system such as the development of lamina-restricted hippocampal connections. Through redox regulation of the actin cytoskeleton controls the intracellular distribution of secretory vesicles containing L1/neurofascin/NgCAM family proteins in neurons, thereby regulating their cell surface levels (By similarity). May act as Rab effector protein and play a role in vesicle trafficking."
## 
## --- LRIG1 ; BF(dB)= 26.99838 24.75076 22.56864 ; M_beta= -0.1905217 -0.1615194 -0.1446158 
##     Leucine Rich Repeats And Immunoglobulin Like Domains 1 
## [1] "Acts as a feedback negative regulator of signaling by receptor tyrosine kinases, through a mechanism that involves enhancement of receptor ubiquitination and accelerated intracellular degradation."
## [2] "By EGF."                                                                                                                                                                                             
## 
## --- MICAL3 ; BF(dB)= 26.99838 23.90843 ; M_beta= 0.10445 0.1188371 
##     Microtubule Associated Monooxygenase, Calponin And LIM Domain Containing 3 
## [1] "Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization. In the absence of actin, it also functions as a NADPH oxidase producing H(2)O(2). Seems to act as Rab effector protein and plays a role in vesicle trafficking. Involved in exocytic vesicles tethering and fusion: the monooxygenase activity is required for this process and implicates RAB8A associated with exocytotic vesicles. Required for cytokinesis. Contributes to stabilization and/or maturation of the intercellular bridge independently of its monooxygenase activity. Promotes recruitment of Rab8 and ERC1 to the intercellular bridge, and together these proteins are proposed to function in timely abscission."
## 
## --- ARVCF ; BF(dB)= 26.93564 ; M_beta= 0.1740567 
##     ARVCF Delta Catenin Family Member 
## [1] "Drosophila armadillo repeat gene homolog,catenin family,ubiquitously expressed,involved in protein-protein interaction at adherens juctions,deleted in the velocardiofacial syndrome"
## [2] "Involved in protein-protein interactions at adherens junctions."                                                                                                                     
## 
## --- FAM161A ; BF(dB)= 26.8735 ; M_beta= -0.1987652 
##     FAM161 Centrosomal Protein A 
## [1] "Involved in ciliogenesis."
## 
## --- SLAMF6 ; BF(dB)= 26.69051 ; M_beta= 0.1827944 
##     SLAM Family Member 6 
## [1] "Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Triggers cytolytic activity only in natural killer cells (NK) expressing high surface densities of natural cytotoxicity receptors (PubMed:11489943, PubMed:16920955). Positive signaling in NK cells implicates phosphorylation of VAV1. NK cell activation seems to depend on SH2D1B and not on SH2D1A (PubMed:16920955). In conjunction with SLAMF1 controls the transition between positive selection and the subsequent expansion and differentiation of the thymocytic natural killer T (NKT) cell lineage (By similarity). Promotes T-cell differentiation into a helper T-cell Th17 phenotype leading to increased IL-17 secretion; the costimulatory activity requires SH2D1A (PubMed:22184727, PubMed:16920955). Promotes recruitment of RORC to the IL-17 promoter (PubMed:22989874). In conjunction with SLAMF1 and CD84/SLAMF5 may be a negative regulator of the humoral immune response. In the absence of SH2D1A/SAP can transmit negative signals to CD4(+) T-cells and NKT cells. Negatively regulates germinal center formation by inhibiting T-cell:B-cell adhesion; the function probably implicates increased association with PTPN6/SHP-1 via ITSMs in absence of SH2D1A/SAP. However, reported to be involved in maintaining B-cell tolerance in germinal centers and in preventing autoimmunity (By similarity)."
## 
## --- UNC5B ; BF(dB)= 26.60087 ; M_beta= 0.119981 
##     Unc-5 Netrin Receptor B 
## [1] "Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion (By similarity). Functions as netrin receptor that negatively regulates vascular branching during angiogenesis. Mediates retraction of tip cell filopodia on endothelial growth cones in response to netrin (By similarity). It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (PubMed:12598906). Mediates apoptosis by activating DAPK1. In the absence of NTN1, activates DAPK1 by reducing its autoinhibitory phosphorylation at Ser-308 thereby increasing its catalytic activity (By similarity)."
## [2] "By p53/TP53."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
## 
## --- HTR6 ; BF(dB)= 26.42508 ; M_beta= -0.1944161 
##     5-Hydroxytryptamine Receptor 6 
## [1] "5-hydroxytrhyptamine (serotonin) receptor,subtype 6,prominently expressed in the caudal nucleus,G protein coupled receptor superfamily,activating adenylate cyclase"                                                                                                                                                                                                                                                                                                                                               
## [2] "This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611)."
## 
## --- CPA1 ; BF(dB)= 26.42508 ; M_beta= -0.1705164 
##     Carboxypeptidase A1 
## [1] "carboxypeptidase A1,pancreatic"                                                                                                                                                                                                                                             
## [2] "Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro (PubMed:8806703). Catalyzes the conversion of leukotriene C4 to leukotriene F4 via the hydrolysis of an amide bond (By similarity)."
## 
## --- MAB21L1 ; BF(dB)= 26.33884 ; M_beta= 0.1090168 
##     Mab-21 Like 1 
## [1] "originally detected in a retina cDNA library,highly expressed in the cerebellum,homolog to the C elegans cell fate determining gene mab-21,with a highly polymorphic CAG repeat(from 5 to 31 triplets),transmitted unstably between generation,exhibiting somatic mosaicism,but not correlated to a clinical phenotype"
## [2] "Putative nucleotidyltransferase required for several aspects of embryonic development including normal development of the eye (PubMed:27103078, PubMed:30487245). It is unclear whether it displays nucleotidyltransferase activity in vivo (PubMed:27271801). Binds single-stranded RNA (ssRNA) (PubMed:27271801)."   
## 
## --- NBEA ; BF(dB)= 26.33884 ; M_beta= 0.1090168 
##     Neurobeachin 
## [1] "neurobeachin,cytosolic protein,specifically expressed in brain,peripherally associated with several membrane compartments including trans-Golgi network and endosome-like structures,may be involved in membrane trafficking events"
## [2] "Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the membrane. May anchor the kinase to cytoskeletal and/or organelle-associated proteins (By similarity)."                                     
## 
## --- PODXL ; BF(dB)= 26.28194 ; M_beta= 0.1550693 
##     Podocalyxin Like 
## [1] "Involved in the regulation of both adhesion and cell morphology and cancer progression. Functions as an anti-adhesive molecule that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion. Acts as a pro-adhesive molecule, enhancing the adherence of cells to immobilized ligands, increasing the rate of migration and cell-cell contacts in an integrin-dependent manner. Induces the formation of apical actin-dependent microvilli. Involved in the formation of a preapical plasma membrane subdomain to set up initial epithelial polarization and the apical lumen formation during renal tubulogenesis. Plays a role in cancer development and aggressiveness by inducing cell migration and invasion through its interaction with the actin-binding protein EZR. Affects EZR-dependent signaling events, leading to increased activities of the MAPK and PI3K pathways in cancer cells."
## [2] "podocalyxin-like protein,integral component of the glomerular epithelial cell glycocalyx"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
## 
## --- DDX18 ; BF(dB)= 26.2255 ; M_beta= 0.1526087 
##     DEAD-Box Helicase 18 
## [1] "Probable RNA-dependent helicase."
## 
## --- ARHGEF18 ; BF(dB)= 26.19745 ; M_beta= 0.1511909 
##     Rho/Rac Guanine Nucleotide Exchange Factor 18 
## [1] "Acts as guanine nucleotide exchange factor (GEF) for RhoA GTPases. Its activation induces formation of actin stress fibers. Also acts as a GEF for RAC1, inducing production of reactive oxygen species (ROS). Does not act as a GEF for CDC42. The G protein beta-gamma (Gbetagamma) subunits of heterotrimeric G proteins act as activators, explaining the integrated effects of LPA and other G-protein coupled receptor agonists on actin stress fiber formation, cell shape change and ROS production. Required for EPB41L4B-mediated regulation of the circumferential actomyosin belt in epithelial cells (PubMed:22006950)."
## 
## --- SCHIP1 ; BF(dB)= 26.11396 ; M_beta= -0.1676593 
##      
## character(0)
## 
## --- SH3RF1 ; BF(dB)= 26.11396 ; M_beta= -0.1943582 
##     SH3 Domain Containing Ring Finger 1 
## [1] "Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination (PubMed:15659549, PubMed:20696164). Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-independent endocytosis (PubMed:19710010). Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4(+) and CD8(+) T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4(+) T-cells and the activation of MAPK8/JNK1 in CD8(+) T-cells. Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (By similarity)."
## [2] "(Microbial infection) Plays an essential role in the targeting of HIV-1 Gag to the plasma membrane, this function is dependent on it's RING domain, and hence it's E3 ligase activity."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
## 
## --- RALGDS ; BF(dB)= 25.86918 ; M_beta= 0.1384358 
##     Ral Guanine Nucleotide Dissociation Stimulator 
## [1] "Stimulates the dissociation of GDP from the Ras-related RalA and RalB GTPases which allows GTP binding and activation of the GTPases. Interacts and acts as an effector molecule for R-Ras, H-Ras, K-Ras, and Rap."
## [2] "Ral guanine nucleotide dissociation stimulator,related protein,115kDa,involved in signal transduction"                                                                                                             
## 
## --- WDPCP ; BF(dB)= 25.73665 ; M_beta= 0.1515942 
##     WD Repeat Containing Planar Cell Polarity Effector 
## [1] "Probable effector of the planar cell polarity signaling pathway which regulates the septin cytoskeleton in both ciliogenesis and collective cell movements. Together with FUZ and WDPCP proposed to function as core component of the CPLANE (ciliogenesis and planar polarity effectors) complex involved in the recruitment of peripheral IFT-A proteins to basal bodies (By similarity)."
## 
## --- FCRL6 ; BF(dB)= 25.6843 ; M_beta= 0.1216471 
##     Fc Receptor Like 6 
## [1] "Acts as a MHC class II receptor (PubMed:20519654). When stimulated on its own, does not play a role in cytokine production or the release of cytotoxic granules by NK cells and cytotoxic CD8(+) T cells (PubMed:17213291, PubMed:18991291). Does not act as an Fc receptor (PubMed:18991291)."
## [2] "Down-regulated upon stimulation with mitogen phytohaemagglutinin (PHA) or concavalin A in peripheral blood mononuclear cells (PBMCs)."                                                                                                                                                         
## 
## --- PDE4B ; BF(dB)= 25.65826 ; M_beta= -0.1780833 
##     Phosphodiesterase 4B 
## [1] "Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes. May be involved in mediating central nervous system effects of therapeutic agents ranging from antidepressants to antiasthmatic and anti-inflammatory agents."
## [2] "Inhibited by rolipram."                                                                                                                                                                                                                                                 
## [3] "cAMP specific nucleotide phosphodiesterase class IV,B,with homology to Drosophila dunce gene,involved in signal transduction"                                                                                                                                           
## 
## --- ATAD2 ; BF(dB)= 25.65826 ; M_beta= -0.1638826 
##     ATPase Family AAA Domain Containing 2 
## [1] "May be a transcriptional coactivator of the nuclear receptor ESR1 required to induce the expression of a subset of estradiol target genes, such as CCND1, MYC and E2F1. May play a role in the recruitment or occupancy of CREBBP at some ESR1 target gene promoters. May be required for histone hyperacetylation. Involved in the estrogen-induced cell proliferation and cell cycle progression of breast cancer cells."
## [2] "Up-regulated in breast, uterus, colon, ovary, and stomach tumors. Induced in breast cancer cells overexpressing NCOA3 or treated with estrogen. Down-regulated in 5-fluorouracil-resistant derivatives of the colon cancer cell line HCT 116."                                                                                                                                                                             
## 
## --- BLOC1S3 ; BF(dB)= 25.6323 ; M_beta= -0.1360895 
##     Biogenesis Of Lysosomal Organelles Complex 1 Subunit 3 
## [1] "Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking."
## 
## --- TRAPPC6A ; BF(dB)= 25.6323 ; M_beta= -0.1360895 
##     Trafficking Protein Particle Complex Subunit 6A 
## [1] "May play a role in vesicular transport during the biogenesis of melanosomes."
## 
## --- MARK4 ; BF(dB)= 25.6323 ; M_beta= -0.1360895 
##     Microtubule Affinity Regulating Kinase 4 
## [1] "Serine/threonine-protein kinase (PubMed:15009667, PubMed:14594945, PubMed:23666762, PubMed:23184942). Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:14594945, PubMed:23666762). Also phosphorylates the microtubule-associated proteins MAP2 and MAP4 (PubMed:14594945). Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles (PubMed:14594945, PubMed:25123532). Required for the initiation of axoneme extension during cilium assembly (PubMed:23400999). Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro (PubMed:23400999). Plays a role in cell cycle progression, specifically in the G1/S checkpoint (PubMed:25123532). Reduces neuronal cell survival (PubMed:15009667). Plays a role in energy homeostasis by regulating satiety and metabolic rate (By similarity). Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (By similarity). Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation (PubMed:23184942)."
## [2] "Activated by phosphorylation on Thr-214."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
## 
## --- ABCA13 ; BF(dB)= 25.1795 ; M_beta= -0.1558507 
##     ATP Binding Cassette Subfamily A Member 13 
## [1] "May mediate the cholesterol and gangliosides transport from the plasma membrane to intracellular vesicles in an ATP hydrolysis dependent manner, thus playing a role in their internalization by endocytic retrograde transport and may also participate in the endocytosis of synaptic vesicle in cortical neurons."
## 
## --- PDE4D ; BF(dB)= 25.15508 ; M_beta= -0.1803929 
##     Phosphodiesterase 4D 
## [1] "Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes."                   
## [2] "Inhibited by rolipram. Activated by phosphatidic acid."                                                                      
## [3] "cAMP specific nucleotide phosphodiesterase class IV,D,with homology to Drosophila dunce gene,involved in signal transduction"
## 
## --- APRT ; BF(dB)= 25.05817 24.40909 ; M_beta= -0.1773996 -0.1649931 
##     Adenine Phosphoribosyltransferase 
## [1] "adenine phosphoribosyltransferase,purine salvage pathway"                                                               
## [2] "Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis."
## 
## --- GALNS ; BF(dB)= 25.05817 24.40909 ; M_beta= -0.1773996 -0.1649931 
##     Galactosamine (N-Acetyl)-6-Sulfatase 
## [1] "acetyl-galactosamine-6-sulfate sulfatase,lysosomal,acting on keratan sulfate,stepwise degradation of glycosaminoglycans (mucopolysaccharides)"
## 
## --- CDT1 ; BF(dB)= 25.05817 24.40909 ; M_beta= -0.1773996 -0.1649931 
##     Chromatin Licensing And DNA Replication Factor 1 
## [1] "Required for both DNA replication and mitosis (PubMed:11125146, PubMed:22581055, PubMed:21856198, PubMed:14993212, PubMed:26842564). DNA replication licensing factor, required for pre-replication complex assembly. Cooperates with CDC6 and the origin recognition complex (ORC) during G1 phase of the cell cycle to promote the loading of the mini-chromosome maintenance (MCM) complex onto DNA to generate pre-replication complexes (pre-RC)(PubMed:14672932). Required also for mitosis by promoting stable kinetochore-microtubule attachments (PubMed:22581055). Potential oncogene (By similarity)."
## [2] "Induced by E2F transcription factors (PubMed:14990995)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
## 
## --- EAPP ; BF(dB)= 24.98622 ; M_beta= -0.1324004 
##     E2F Associated Phosphoprotein 
## [1] "May play an important role in the fine-tuning of both major E2F1 activities, the regulation of the cell-cycle and the induction of apoptosis. Promotes S-phase entry, and inhibits p14(ARP) expression."
## 
## --- NEK7 ; BF(dB)= 24.9386 ; M_beta= -0.1560042 
##     NIMA Related Kinase 7 
## [1] "Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:17101132). Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis (PubMed:17586473, PubMed:19414596). Phosphorylates RPS6KB1 (By similarity). Phosphorylates EML4 at 'Ser-146', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757)."
## [2] "Binding to NEK9 stimulates its activity by releasing the autoinhibitory function of Tyr-97."                                                                                                                                                                                                                                                                                                                                                                           
## 
## --- AGO3 ; BF(dB)= 24.89125 ; M_beta= -0.1483993 
##     Argonaute RISC Catalytic Component 3 
## [1] "Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Proposed to be involved in stabilization of small RNA derivates (siRNA) derived from processed RNA polymerase III-transcribed Alu repeats containing a DR2 retinoic acid response element (RARE) in stem cells and in the subsequent siRNA-dependent degradation of a subset of RNA polymerase II-transcribed coding mRNAs by recruiting a mRNA decapping complex involving EDC4. Possesses RNA slicer activity but only on select RNAs bearing 5'- and 3'-flanking sequences to the region of guide-target complementarity (PubMed:29040713)."
## 
## --- ZNF469 ; BF(dB)= 24.86767 ; M_beta= -0.1623525 
##     Zinc Finger Protein 469 
## [1] "May be involved in transcriptional regulation."
## 
## --- CRY1 ; BF(dB)= 24.86767 ; M_beta= 0.06063365 
##     Cryptochrome Circadian Regulator 1 
## [1] "cryptochrome 1,photolyase-like,66kDa,putatively involved in photoreactivation,i.e DNA repair by excision of UV induced DNA damage"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
## [2] "Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. CRY1 and CRY2 have redundant functions but also differential and selective contributions at least in defining the pace of the SCN circadian clock and its circadian transcriptional outputs. More potent transcriptional repressor in cerebellum and liver than CRY2, though more effective in lengthening the period of the SCN oscillator. On its side, CRY2 seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY2, is dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus. Interacts with CLOCK-ARNTL/BMAL1 independently of PER proteins and is found at CLOCK-ARNTL/BMAL1-bound sites, suggesting that CRY may act as a molecular gatekeeper to maintain CLOCK-ARNTL/BMAL1 in a poised and repressed state until the proper time for transcriptional activation. Represses the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1. Represses the CLOCK-ARNTL/BMAL1 induced transcription of ATF4, MTA1, KLF10 and NAMPT (By similarity). May repress circadian target genes expression in collaboration with HDAC1 and HDAC2 through histone deacetylation. Mediates the clock-control activation of ATR and modulates ATR-mediated DNA damage checkpoint. In liver, mediates circadian regulation of cAMP signaling and gluconeogenesis by binding to membrane-coupled G proteins and blocking glucagon-mediated increases in intracellular cAMP concentrations and CREB1 phosphorylation. Inhibits hepatic gluconeogenesis by decreasing nuclear FOXO1 levels that downregulates gluconeogenic gene expression (By similarity). Besides its role in the maintenance of the circadian clock, is also involved in the regulation of other processes. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by binding to glucocorticoid response elements (GREs). Plays a key role in glucose and lipid metabolism modulation, in part, through the transcriptional regulation of genes involved in these pathways, such as LEP or ACSL4 (By similarity). Represses PPARD and its target genes in the skeletal muscle and limits exercise capacity (By similarity). Plays an essential role in the generation of circadian rhythms in the retina (By similarity). Represses the transcriptional activity of NR1I2 (By similarity)."
## [3] "Expression is regulated by light and circadian rhythms and osicllates diurnally. Peak expression in the suprachiasma nucleus (SCN) and eye at the day/night transition (CT12). Levels decrease with ARNTL/BMAL1-CLOCK inhibition as part of the autoregulatory feedback loop."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
## [4] "KL001 (N-[3-(9H-carbazol-9-yl)-2-hydroxypropyl]-N-(2-furanylmethyl)-methanesulfonamide) binds to CRY1 and stabilizes it by inhibiting FBXL3- and ubiquitin-dependent degradation of CRY1 resulting in lengthening of the circadian periods."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
## 
## --- SIGIRR ; BF(dB)= 24.79733 ; M_beta= -0.167444 
##     Single Ig And TIR Domain Containing 
## [1] "Acts as a negative regulator of the Toll-like and IL-1R receptor signaling pathways. Attenuates the recruitment of receptor-proximal signaling components to the TLR4 receptor, probably through an TIR-TIR domain interaction with TLR4. Through its extracellular domain interferes with the heterodimerization of Il1R1 and IL1RAP."
## [2] "Down-regulated during inflammation by inhibition of an SP1-mediated pathway."                                                                                                                                                                                                                                                          
## 
## --- ABCA8 ; BF(dB)= 24.77401 ; M_beta= 0.1745317 
##     ATP Binding Cassette Subfamily A Member 8 
## [1] "[Isoform 1]: Catalyzes the import of organic anions such as taurocholate and estrone sulfate in an ATP-dependent manner (PubMed:12379217). In vitro, also imports ochratoxin A (PubMed:12379217). In addition mediates the cholesterol efflux in an apolipoprotein independent manner an plays a role in sphingomyelin production in oligodendrocytes (PubMed:23560799)."                       
## [2] "[Isoform 3]: Catalyzes the cholesterol and taurocholate efflux in an ATP-dependent manner (PubMed:29300488). Through the interaction with ABCA1 potentiates the cholesterol efflux to lipid-free APOA1, in turn regulates high-density lipoprotein cholesterol levels (PubMed:28882873)."                                                                                                       
## [3] "[Isoform 1]: Kinetic parameters: KM=30.4 uM for estradiol-beta-glucuronide {ECO:0000269|PubMed:12379217}; KM=0.1 uM for LTC4 {ECO:0000269|PubMed:12379217}; KM=10.3 uM for taurochlorate {ECO:0000269|PubMed:12379217}; KM=5.0 uM for PAH {ECO:0000269|PubMed:12379217}; KM=0.5 uM for estrone sulfate {ECO:0000269|PubMed:12379217}; KM=0.4 uM for ochratoxin A {ECO:0000269|PubMed:12379217};"
## [4] "[Isoform 1]: Dofequidar (MS-209) and ochratoxin A inhibited the 17beta-estradiol 17-O-(beta-D-glucuronate) infflux."                                                                                                                                                                                                                                                                            
## [5] "[Isoform 3]: Cholesterol efflux is increased by extracellularly applied taurocholate."                                                                                                                                                                                                                                                                                                          
## 
## --- UNC80 ; BF(dB)= 24.75076 ; M_beta= -0.1887222 
##     Unc-80 Homolog, NALCN Channel Complex Subunit 
## [1] "Component of the NALCN sodium channel complex, required for channel regulation. This complex is a cation channel activated by neuropeptides substance P, neurotensin, and extracellular calcium that regulates neuronal excitability by controlling the sizes of NALCN-dependent sodium-leak current. UNC80 is essential for NALCN sensitivity to extracellular calcium."
## 
## --- SBNO1 ; BF(dB)= 24.70443 ; M_beta= -0.1722199 
##      
## character(0)
## 
## --- PIK3C2G ; BF(dB)= 24.68136 ; M_beta= 0.1131184 
##     Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Gamma 
## [1] "phosphatidylinositol 3-kinase class 2,gamma polypeptide,expressed in normal breast,liver,prostate and other tissues"                                                                                           
## [2] "Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. May play a role in SDF1A-stimulated chemotaxis (By similarity)."
## 
## --- PNPT1 ; BF(dB)= 24.58968 ; M_beta= -0.1833238 
##     Polyribonucleotide Nucleotidyltransferase 1 
## [1] "RNA-binding protein implicated in numerous RNA metabolic processes. Catalyzes the phosphorolysis of single-stranded polyribonucleotides processively in the 3'-to-5' direction. Mitochondrial intermembrane factor with RNA-processing exoribonulease activity. Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. Involved in the degradation of non-coding mitochondrial transcripts (MT-ncRNA) and tRNA-like molecules (PubMed:29967381). Required for correct processing and polyadenylation of mitochondrial mRNAs. Plays a role as a cytoplasmic RNA import factor that mediates the translocation of small RNA components, like the 5S RNA, the RNA subunit of ribonuclease P and the mitochondrial RNA-processing (MRP) RNA, into the mitochondrial matrix. Plays a role in mitochondrial morphogenesis and respiration; regulates the expression of the electron transport chain (ETC) components at the mRNA and protein levels. In the cytoplasm, shows a 3'-to-5' exoribonuclease mediating mRNA degradation activity; degrades c-myc mRNA upon treatment with IFNB1/IFN-beta, resulting in a growth arrest in melanoma cells. Regulates the stability of specific mature miRNAs in melanoma cells; specifically and selectively degrades miR-221, preferentially. Plays also a role in RNA cell surveillance by cleaning up oxidized RNAs. Binds to the RNA subunit of ribonuclease P, MRP RNA and miR-221 microRNA."
## [2] "Up-regulated in cells upon senescence and terminal differentiation. Up-regulated after treatment with IFNB1/IFN-beta."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
## 
## --- TTL ; BF(dB)= 24.47639 ; M_beta= 0.1524744 
##     Tubulin Tyrosine Ligase 
## [1] "tetracycline transporter-like"                                                                                
## [2] "Catalyzes the post-translational addition of a tyrosine to the C-terminal end of detyrosinated alpha-tubulin."
## 
## --- ALS2 ; BF(dB)= 24.4539 ; M_beta= -0.1391 
##     Alsin Rho Guanine Nucleotide Exchange Factor ALS2 
## [1] "May act as a GTPase regulator. Controls survival and growth of spinal motoneurons (By similarity)."
## 
## --- EQTN ; BF(dB)= 24.3645 ; M_beta= 0.1233488 
##     Equatorin 
## [1] "Acrosomal membrane-anchored protein involved in the process of fertilization and in acrosome biogenesis."
## 
## --- ZNF350 ; BF(dB)= 24.298 ; M_beta= 0.1719766 
##     Zinc Finger Protein 350 
## [1] "Transcriptional repressor. Binds to a specific sequence, 5'-GGGxxxCAGxxxTTT-3', within GADD45 intron 3."
## 
## --- SGTA ; BF(dB)= 24.16641 ; M_beta= -0.1678886 
##     Small Glutamine Rich Tetratricopeptide Repeat Co-Chaperone Alpha 
## [1] "Co-chaperone that binds misfolded and hydrophobic patches-containing client proteins in the cytosol. Mediates their targeting to the endoplasmic reticulum but also regulates their sorting to the proteasome when targeting fails (PubMed:28104892). Functions in tail-anchored/type II transmembrane proteins membrane insertion constituting with ASNA1 and the BAG6 complex a targeting module (PubMed:28104892). Functions upstream of the BAG6 complex and ASNA1, binding more rapidly the transmembrane domain of newly synthesized proteins (PubMed:28104892, PubMed:25535373). It is also involved in the regulation of the endoplasmic reticulum-associated misfolded protein catabolic process via its interaction with BAG6: collaborates with the BAG6 complex to maintain hydrophobic substrates in non-ubiquitinated states (PubMed:23129660, PubMed:25179605). Competes with RNF126 for interaction with BAG6, preventing the ubiquitination of client proteins associated with the BAG6 complex (PubMed:27193484). Binds directly to HSC70 and HSP70 and regulates their ATPase activity (PubMed:18759457)."
## [2] "(Microbial infection) In case of infection by polyomavirus, involved in the virus endoplasmic reticulum membrane penetration and infection via interaction with DNAJB12, DNAJB14 and HSPA8/Hsc70 (PubMed:24675744)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
## 
## --- COPA ; BF(dB)= 24.0581 ; M_beta= 0.09751946 
##     COPI Coat Complex Subunit Alpha 
## [1] "Golgi coatomer complex alpha subunit,component of the coat of the non-clathrin-coated vesicles,expressed in a wide range of fetal and adult tissues,homolog to the alpha subunit of S cerevisiae coatomer protein complex,involved in the transport  between the endoplasmic reticulum and Golgi"                                                                                                                                                                                                                                                                                                                                                                                                                             
## [2] "The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors (By similarity)."
## [3] "Xenin stimulates exocrine pancreatic secretion. It inhibits pentagastrin-stimulated secretion of acid, to induce exocrine pancreatic secretion and to affect small and large intestinal motility. In the gut, xenin interacts with the neurotensin receptor."                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
## 
## --- FNDC3B ; BF(dB)= 24.03658 ; M_beta= -0.1483143 
##     Fibronectin Type III Domain Containing 3B 
## [1] "May be a positive regulator of adipogenesis."
## 
## --- AVIL ; BF(dB)= 23.99368 ; M_beta= -0.161289 
##     Advillin 
## [1] "Ca(2+)-regulated actin-binding protein which plays an important role in actin bundling (PubMed:29058690). May have a unique function in the morphogenesis of neuronal cells which form ganglia. Required for SREC1-mediated regulation of neurite-like outgrowth. Plays a role in regenerative sensory axon outgrowth and remodeling processes after peripheral injury in neonates. Involved in the formation of long fine actin-containing filopodia-like structures in fibroblast. Plays a role in ciliogenesis. In podocytes, controls lamellipodia formation through the regulation of EGF-induced diacylglycerol generation by PLCE1 and ARP2/3 complex assembly (PubMed:29058690)."
## 
## --- TSFM ; BF(dB)= 23.99368 ; M_beta= -0.161289 
##     Ts Translation Elongation Factor, Mitochondrial 
## [1] "Associates with the EF-Tu.GDP complex and induces the exchange of GDP to GTP. It remains bound to the aminoacyl-tRNA.EF-Tu.GTP complex up to the GTP hydrolysis stage on the ribosome."
## 
## --- FICD ; BF(dB)= 23.86607 ; M_beta= -0.1475039 
##     FIC Domain Protein Adenylyltransferase 
## [1] "Protein that can both mediate the addition of adenosine 5'-monophosphate (AMP) to specific residues of target proteins (AMPylation), and the removal of the same modification from target proteins (de-AMPylation), depending on the context (By similarity). The side chain of Glu-231 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place (By similarity). Acts as a key regulator of the ERN1/IRE1-mediated unfolded protein response (UPR) by mediating AMPylation or de-AMPylation of HSPA5/BiP (PubMed:25601083). In unstressed cells, acts as an adenylyltransferase by mediating AMPylation of HSPA5/BiP at 'Thr-518', thereby inactivating it (By similarity). In response to endoplasmic reticulum stress, acts as a phosphodiesterase by mediating removal of ATP (de-AMPylation) from HSPA5/BiP at 'Thr-518', leading to restore HSPA5/BiP activity (By similarity). Although it is able to AMPylate RhoA, Rac and Cdc42 Rho GTPases in vitro, Rho GTPases do not constitute physiological substrates (PubMed:19362538, PubMed:25601083)."
## [2] "Up-regulated in response to activation of unfolded protein response (UPR)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
## [3] "The side chain of Glu-234 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-234 binds ATP and competes with ATP-binding at Arg-374, thereby preventing adenylyltransferase activity (PubMed:22266942, PubMed:25435325). In unstressed cells, disengagement of Glu-234 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-234, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (PubMed:22266942, PubMed:25435325)."                                                                                                                                                                                                                                                               
## 
## --- SUN2 ; BF(dB)= 23.84496 ; M_beta= -0.1446258 
##     Sad1 And UNC84 Domain Containing 2 
## [1] "As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex, involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Specifically, SYNE2 and SUN2 assemble in arrays of transmembrane actin-associated nuclear (TAN) lines which are bound to F-actin cables and couple the nucleus to retrograde actin flow during actin-dependent nuclear movement. Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration. Required for nuclear migration in retinal photoreceptor progenitors implicating association with cytoplasmic dynein-dynactin and kinesin motor complexes, and probably B-type lamins; SUN1 and SUN2 seem to act redundantly. The SUN1/2:KASH5 LINC complex couples telomeres to microtubules during meiosis; SUN1 and SUN2 seem to act at least partial redundantly. Anchors chromosome movement in the prophase of meiosis and is involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis. Required for telomere attachment to nuclear envelope and gametogenesis. May also function on endocytic vesicles as a receptor for RAB5-GDP and participate in the activation of RAB5."
## 
## --- TOP3A ; BF(dB)= 23.76093 ; M_beta= 0.09034254 
##     DNA Topoisomerase III Alpha 
## [1] "DNA topoisomerase III,putatively involved in suppression of mitotic recombination between repetitive sequences,deleted in SMCR"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
## [2] "Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone. As an essential component of the RMI complex it is involved in chromosome separation and the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Has DNA decatenation activity (PubMed:30057030). It is required for mtDNA decatenation and segregation after completion of replication, in a process that does not require BLM, RMI1 and RMI2 (PubMed:29290614)."
## 
## --- CAMKK2 ; BF(dB)= 23.74002 ; M_beta= -0.1478707 
##     Calcium/Calmodulin Dependent Protein Kinase Kinase 2 
## [1] "calcium/calmodulin-dependent protein kinase,kinase 2,beta,expressed as a flag-tagged protein in human non small cell lung cancer"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
## [2] "Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade involved in a number of cellular processes. Isoform 1, isoform 2 and isoform 3 phosphorylate CAMK1 and CAMK4. Isoform 3 phosphorylates CAMK1D. Isoform 4, isoform 5 and isoform 6 lacking part of the calmodulin-binding domain are inactive. Efficiently phosphorylates 5'-AMP-activated protein kinase (AMPK) trimer, including that consisting of PRKAA1, PRKAB1 and PRKAG1. This phosphorylation is stimulated in response to Ca(2+) signals (By similarity). Seems to be involved in hippocampal activation of CREB1 (By similarity). May play a role in neurite growth. Isoform 3 may promote neurite elongation, while isoform 1 may promoter neurite branching."
## [3] "[Isoform 1]: Up-regulated by PKA pathway."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
## [4] "Activated by Ca(2+)/calmodulin. Binding of calmodulin may relieve intrasteric autoinhibition. Autophosphorylation does not alter activity or regulation by Ca(2+)/calmodulin. In part, activity is independent on Ca(2+)/calmodulin (By similarity)."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
## 
## --- PARP1 ; BF(dB)= 23.74002 ; M_beta= 0.1286772 
##     Poly(ADP-Ribose) Polymerase 1 
## [1] "Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:25043379, PubMed:33186521, PubMed:32028527, PubMed:26344098). Mediates glutamate, aspartate, serine or tyrosine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:7852410, PubMed:9315851, PubMed:19764761, PubMed:25043379, PubMed:28190768, PubMed:29954836). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:33186521). Mainly mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1 (PubMed:19764761, PubMed:25043379). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP1 active site (PubMed:28190768, PubMed:29954836, PubMed:33186521, PubMed:32028527). Also catalyzes tyrosine ADP-ribosylation of target proteins following interaction with HPF1 (PubMed:30257210, PubMed:29954836). PARP1 initiates the repair of DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones, thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:17177976, PubMed:18172500, PubMed:19344625, PubMed:19661379, PubMed:23230272, PubMed:27067600). In addition to base excision repair (BER) pathway, also involved in double-strand breaks (DSBs) repair: together with TIMELESS, accumulates at DNA damage sites and promotes homologous recombination repair by mediating poly-ADP-ribosylation (PubMed:26344098, PubMed:30356214). Mediates the poly(ADP-ribosyl)ation of a number of proteins, including itself, APLF and CHFR (PubMed:17396150, PubMed:19764761). In addition to proteins, also able to ADP-ribosylate DNA: catalyzes ADP-ribosylation of DNA strand break termini containing terminal phosphates and a 2'-OH group in single- and double-stranded DNA, respectively (PubMed:27471034). Required for PARP9 and DTX3L recruitment to DNA damage sites (PubMed:23230272). PARP1-dependent PARP9-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272). Acts as a regulator of transcription: positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150 (PubMed:19344625). Plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and EEF1A1 (PubMed:17177976). Involved in the synthesis of ATP in the nucleus, together with NMNAT1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257)."
## 
## --- PTPRH ; BF(dB)= 23.26992 ; M_beta= -0.1140203 
##     Protein Tyrosine Phosphatase Receptor Type H 
## [1] "protein tyrosine phosphatase,receptor type III,eta polypeptide"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
## [2] "Protein phosphatase that may contribute to contact inhibition of cell growth and motility by mediating the dephosphorylation of focal adhesion-associated substrates and thus negatively regulating integrin-promoted signaling processes. Induces apoptotic cell death by at least two distinct mechanisms: inhibition of cell survival signaling mediated by PI 3-kinase, Akt, and ILK and activation of a caspase-dependent proapoptotic pathway. Inhibits the basal activity of LCK and its activation in response to TCR stimulation and TCR-induced activation of MAP kinase and surface expression of CD69. Inhibits TCR-induced tyrosine phosphorylation of LAT and ZAP70. Inhibits both basal activity of DOK1 and its CD2-induced tyrosine phosphorylation. Induces dephosphorylation of BCAR1, focal adhesion kinase and SRC. Reduces migratory activity of activity of Jurkat cells. Reduces tyrosine phosphorylation of CEACAM20 and thereby contributes to suppress the intestinal immune response CEACAM20 (By similarity)."
## [3] "Induced at the early stage of hepatocellular carcinoma and is suppressed at later stages."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
## [4] "Regulated by reversible dimerization. Dimerization reduces its catalytic activity."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
## 
## --- CPVL ; BF(dB)= 23.03196 ; M_beta= -0.1480427 
##     Carboxypeptidase Vitellogenic Like 
## [1] "May be involved in the digestion of phagocytosed particles in the lysosome, participation in an inflammatory protease cascade, and trimming of peptides for antigen presentation."
## 
## --- GNAS ; BF(dB)= 22.91464 ; M_beta= 0.1258215 
##     GNAS Complex Locus 
## [1] "May inhibit the adenylyl cyclase-stimulating activity of guanine nucleotide-binding protein G(s) subunit alpha which is produced from the same locus in a different open reading frame."                                                                                                                                                                                                                                                                                                                    
## [2] "Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP. GNAS functions downstream of several GPCRs, including beta-adrenergic receptors. XLas isoforms interact with the same set of receptors as GNAS isoforms (By similarity)."                                                  
## [3] "Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs) (PubMed:17110384). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP (PubMed:26206488, PubMed:8702665). GNAS functions downstream of several GPCRs, including beta-adrenergic receptors (PubMed:21488135). Stimulates the Ras signaling pathway via RAPGEF2 (PubMed:12391161)."
## 
## --- ESRRB ; BF(dB)= 22.70219 ; M_beta= 0.09593061 
##     Estrogen Related Receptor Beta 
## [1] "[Isoform 3]: Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity (PubMed:17920186, PubMed:19755138). Plays a role, in a LIF-independent manner, in maintainance of self-renewal and pluripotency of embryonic and trophoblast stem cells through different signaling pathways including FGF signaling pathway and Wnt signaling pathways. Upon FGF signaling pathway activation, interacts with KDM1A by directly binding to enhancer site of ELF5 and EOMES and activating their transcription leading to self-renewal of trophoblast stem cells. Also regulates expression of multiple rod-specific genes and is required for survival of this cell type (By similarity). Plays a role as transcription factor activator of GATA6, NR0B1, POU5F1 and PERM1 (PubMed:23836911). Plays a role as transcription factor repressor of NFE2L2 transcriptional activity and ESR1 transcriptional activity (PubMed:17920186, PubMed:19755138). During mitosis remains bound to a subset of interphase target genes, including pluripotency regulators, through the canonical ESRRB recognition (ERRE) sequence, leading to their transcriptional activation in early G1 phase. Can coassemble on structured DNA elements with other transcription factors like SOX2, POU5F1, KDM1A and NCOA3 to trigger ESRRB-dependent gene activation. This mechanism, in the case of SOX2 corecruitment prevents the embryonic stem cells (ESCs) to epiblast stem cells (EpiSC) transition through positive regulation of NR0B1 that inhibits the EpiSC transcriptional program. Also plays a role inner ear development by controlling expression of ion channels and transporters and in early placentation (By similarity)."
## [2] "[Isoform 1]: Transcription factor that binds a canonical ESRRB recognition (ERRE) sequence 5'TCAAGGTCA-3' localized on promoter and enhancer of targets genes regulating their expression or their transcription activity. Positively regulates ESR1 transcriptional activity upon E2 stimulation."                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
## [3] "estrogen-related receptor B,widely expressed,orphan receptor family,steroid/thyroid hormone receptor superfamily,repressing glucocorticoid receptor activity in a cell specific fashion"                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
## 
## --- P2RX4 ; BF(dB)= 22.58765 ; M_beta= -0.136649 
##     Purinergic Receptor P2X 4 
## [1] "purinoceptor,P2X4,ionotropic class,expressed in heart and spinal cord"                                                       
## [2] "Receptor for ATP that acts as a ligand-gated ion channel. This receptor is insensitive to the antagonists PPADS and suramin."
## 
## --- ZNF467 ; BF(dB)= 22.58765 ; M_beta= -0.1338719 
##     Zinc Finger Protein 467 
## [1] "Transcription factor that promotes adipocyte differentiation and suppresses osteoblast differentiation in the bone marrow. Enhances the osteoclast-supporting ability of stromal cells. Binds with STAT3 the consensus sequence 5'-CTTCTGGGAAGA-3' of the acute phase response element (APRE). Transactivates several promoters including FOS, OSM and PPARG. Recruits a histone deacetylase complex (By similarity)."
## 
## --- SLC25A26 ; BF(dB)= 22.56864 ; M_beta= -0.1446158 
##     Solute Carrier Family 25 Member 26 
## [1] "Mitochondrial solute carriers shuttle metabolites, nucleotides, and cofactors through the mitochondrial inner membrane. Specifically mediates the transport of S-adenosylmethionine (SAM) into the mitochondria."
## [2] "Strongly inhibited by tannic acid and Bromocresol Purple."                                                                                                                                                       
## 
## --- MRPS34 ; BF(dB)= 22.54967 ; M_beta= -0.1255366 
##     Mitochondrial Ribosomal Protein S34 
## [1] "Required for mitochondrial translation, plays a role in maintaining the stability of the small ribosomal subunit and the 12S rRNA that are required for mitoribosome formation."
## 
## --- NME3 ; BF(dB)= 22.54967 ; M_beta= -0.1255366 
##     NME/NM23 Nucleoside Diphosphate Kinase 3 
## [1] "non-metastatic cells 3,protein,with a nm23 nucleoside diphosphate kinase gene family,preferentially expressed at early stage of myeloid differentiation,involved in the  phosphorylation of nucleoside diphophates,inhibiting granulocyte differentiation and inducing apoptosis"                                                         
## [2] "Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Probably has a role in normal hematopoiesis by inhibition of granulocyte differentiation and induction of apoptosis."
## 
## --- EME2 ; BF(dB)= 22.54967 ; M_beta= -0.1255366 
##     Essential Meiotic Structure-Specific Endonuclease Subunit 2 
## [1] "Interacts with MUS81 to form a DNA structure-specific endonuclease which cleaves substrates such as 3'-flap structures."
## 
## --- SPSB3 ; BF(dB)= 22.54967 ; M_beta= -0.1255366 
##     SplA/Ryanodine Receptor Domain And SOCS Box Containing 3 
## [1] "May be a substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins."
## 
## --- w  missing genes
## [1] "SEPT1"    "ASNA1"    "C19ORF43" "SCHIP1"   "SBNO1"